Using normative modeling to assess pharmacological treatment effect on brain state in patients with schizophrenia.

Quantifying individual differences in neuroimaging metrics is attracting interest in clinical studies with mental disorders. Schizophrenia is diagnosed exclusively based on symptoms, and the biological heterogeneity makes it difficult to accurately assess pharmacological treatment effects on the brain state. Using the Cambridge Centre for Ageing and Neuroscience data set, we built normative models of brain states and mapped the deviations of the brain characteristics of each patient, to test whether deviations were related to symptoms, and further investigated the pharmacological treatment effect on deviation distributions. Specifically, we found that the patients can be divided into 2 groups: the normalized group had a normalization trend and milder symptoms at baseline, and the other group showed a more severe deviation trend. The baseline severity of the depression as well as the overall symptoms could predict the deviation of the static characteristics for the dorsal and ventral attention networks after treatment. In contrast, the positive symptoms could predict the deviations of the dynamic fluctuations for the default mode and dorsal attention networks after treatment. This work evaluates the effect of pharmacological treatment on static and dynamic brain states using an individualized approach, which may assist in understanding the heterogeneity of the illness pathology as well as the treatment response.

Advance in the pharmacological and comorbidities management of heart failure with preserved ejection fraction: evidence from clinical trials.

The prevalence of heart failure with preserved ejection fraction (HFpEF) accounts for approximately 50% of the total heart failure population, and with the aging of the population and the increasing prevalence of hypertension, obesity, and type 2 diabetes (T2DM), the incidence of HFpEF continues to rise and has become the most common subtype of heart failure. Compared with heart failure with reduced ejection fraction, HFpEF has a more complex pathophysiology and is more often associated with hypertension, T2DM, obesity, atrial fibrillation, renal insufficiency, pulmonary hypertension, obstructive sleep apnea, and other comorbidities. HFpEF has generally been considered a syndrome with high phenotypic heterogeneity, and no effective treatments have been shown to reduce mortality to date. Diuretics and comorbidity management are traditional treatments for HFpEF; however, they are mostly empirical due to a lack of clinical evidence in the setting of HFpEF. With the EMPEROR-Preserved and DELIVER results, sodium-glucose cotransporter 2 inhibitors become the first evidence-based therapies to reduce rehospitalization for heart failure. Subgroup analyses of the PARAGON-HF, TOPCAT, and CHARM-Preserved trials suggest that angiotensin receptor-neprilysin inhibitors, spironolactone, and angiotensin II receptor blockers may be beneficial in patients at the lower end of the ejection fraction spectrum. Other potential pharmacotherapies represented by non-steroidal mineralocorticoid receptor antagonists finerenone and antifibrotic agent pirfenidone also hold promise for the treatment of HFpEF. This article intends to review the clinical evidence on current pharmacotherapies of HFpEF, as well as the comorbidities management of atrial fibrillation, hypertension, T2DM, obesity, pulmonary hypertension, renal insufficiency, obstructive sleep apnea, and iron deficiency, to optimize the clinical management of HFpEF.

Pharmacological and Non-Pharmacological Advancements in Heart Failure Treatment.

Heart failure (HF) is a complex, life-threatening condition characterized by high mortality, morbidity, and poor quality of life. Despite studies of epidemiology, pathogenesis, and therapies, the rate of HF hospitalization is still increasing due to the growing and aging population and an increase in obesity in relatively younger individuals. It remains a predominant issue in the public health and the global economic burden. Current research has focused on how HF affects the entire range of left ventricular ejection fraction (LVEF), especially the three HF subgroups. This review provides a latest overview of pharmacological and non-pharmacological strategies of these three subgroups (HF with preserved ejection fraction, HF with reduced ejection fraction, and HF with mildly reduced ejection fraction). We summarize conventional therapies, investigate novel strategies, and explore the new technologies such as aortic thoracic stimulation and interatrial shunting devices.

Positive effect of deep diaphragmatic breathing training on gastroesophageal reflux-induced chronic cough: a clinical randomized controlled study.

BACKGROUND AND OBJECTIVE: To explore the efficacy of deep diaphragmatic breathing training (DEP) in patients with gastroesophageal reflux-induced chronic cough (GERC). METHODS: A randomized controlled study was conducted involving 60 GERC patients who were divided into the intervention group and the control group (each with 30 patients). Both groups received routine medication treatment for GERC, while the intervention group received DEP training additionally. Both groups were evaluated by cough symptom scores, Hull airway reflux questionnaire (HARQ), gastroesophageal reflux diagnostic questionnaire (GerdQ), generalized anxiety disorder scale-7 (GAD-7), patient health questionnaire-9 (PHQ-9), Pittsburgh sleep quality index (PSQI), the Leicester cough questionnaire (LCQ), as well as capsaicin cough sensitivity testing, B-ultrasound and surface electromyography (sEMG) of the diaphragmatic muscles before and after treatment. The cough resolution rate and changes of the above indictors was compared between the two groups after eight weeks of treatment. RESULTS: After eight weeks of treatment, cough symptoms improved in both groups, but the cough resolution rate in the intervention group of 94% was significantly higher than that in the control group of 77% (χ2 = 6.402, P = 0.041). The intervention group showed significant improvements to the control group in GerdQ (6.13(0.35) VS 6.57(0.77)), GAD-7 (0(0;1) VS 1(0;3)), PSQI (2(1;3) VS 4(3;6)), LCQ (17.19(1.56) VS 15.88(1.92)) and PHQ-9 (0(0;0) VS 0(0;3)) after treatment. Compared to control group, sEMG activity of the diaphragmatic muscle was significantly increased in the intervention group after treatment, measured during DEP (79.00(2.49) VS 74.65 (1.93)) and quiet breathing (72.73 (1.96) VS 67.15 (2.48)). CONCLUSION: DEP training can improve cough symptoms as an adjunctive treatment in GERC patients. TRIAL REGISTRATION: The protocol was registered in February 2, 2022 via the Chinese Clinical Trials Register ( http://www.chictr.org.cn/ ) [ChiCTR2200056246].

Topiramate use in a pediatric patient with comorbid bipolar disorder and trichotillomania: A 3-year follow-up.

Trichotillomania (TTM) is an intractable and chronic mental disorder that causes significant distress or functional impairments in various life domains. Most individuals with trichotillomania have other comorbid diagnoses. Bipolar disorder (BD) is one of the most common comorbid conditions. Up to date, no FDA-approved drugs for TTM are available, not to mention children and adolescent patients with TTM and BD. Here, we present a case of an 8-year-old child with a long history of episodic TTM and bipolar disorder who was effectively treated with topiramate in a 3-year follow-up.

Multidisciplinary care in Parkinson's disease.

Parkinson's Disease (PD) is a multifaceted and progressive disorder characterized by a diverse range of motor and non-motor symptoms. The complexity of PD necessitates a multidisciplinary approach to manage both motor symptoms, such as bradykinesia, gait disturbances and falls, and non-motor symptoms, including cognitive dysfunction, sleep disturbances, and mood disorders, which significantly affect patients' quality of life. Pharmacotherapy, particularly dopaminergic replacement therapy, has advanced to alleviate many symptoms. However, these medications can also induce side effects or aggravate symptoms like hallucinations or orthostatic dysfunction, highlighting the need for comprehensive patient management. The optimal care for PD patients involves a team of specialists, including neurologists, physical and occupational therapists, speech-language pathologists, psychologists, and other medical professionals, to address the complex and individualized needs of each patient. Here, we illustrate the necessity of such a multidisciplinary approach in four illustrative PD cases with different disease stages and motor and non-motor complications. The patients were treated in different treatment settings (specialized outpatient clinic, day clinic, inpatient care including neurorehabilitation). The biggest challenge lies in organizing and implementing such comprehensive care effectively across different clinical settings.

Emerging drugs in phase II and III clinical development for the treatment of alcohol use disorder.

INTRODUCTION: Alcohol Use Disorder (AUD) poses an ongoing significant global health burden. AUD is highly prevalent and affects not only the individuals with AUD, but also their communities and society at large. Even though pharmacotherapy is an integral part of AUD treatment, the few available substances show limited efficacy and limited clinical impact. Thus, there is a need for new innovative pharmacotherapeutic approaches. AREAS COVERED: This paper provides a comprehensive review of drugs approved for the treatment of AUD as well as those currently in phase II and III development. Data from recent clinical trials has been reviewed and supplemented by additional literature based on a systematic search of the PubMed database and clinical trials registries. Compounds discussed include disulfiram, naltrexone, nalmefene, acamprosat, baclofen, sodium oxybate, doxazosin, varenicline, zonisamide, gabapentin, apremilast, ibudilast, ivermectin, tolcapone, mifepristone, suvorexant, ketamine, psilocybin, semaglutide, oxytocin and cannabidiol. EXPERT OPINION: Even though the majority of the discussed compounds lack sufficient evidence to support their efficacy, multiple promising new treatment options are currently under investigation. Future research has to consider specific phenotypes and subgroups of AUD as well as a possible enhancement of the effects of psychotherapy through combination with pharmacotherapy. Practitioners should be encouraged to use available compounds to support existing therapeutic regimens.

Discordances in patients' and physicians' perspectives on which contextual factors should be accounted for during smoking cessation.

BACKGROUND: Smoking cessation interventions requires attending to the circumstances and needs of individual patients. We aimed at highlighting the discordances between patients' and physicians' perspectives on contextual factors that should be considered during smoking cessation. METHODS: We identified 36 contextual factors identified that should be considered during smoking cessation using PubMed and interviewing general practitioners. Physicians recruited through social networks campaigns and smoker or former smoker patients from the ComPaRe cohort selected the factors they considered most relevant in two online paired comparison experiment. Bradley Terry Luce models estimated the ability of each factor (i.e. the probability to be preferred). We calculated the Pearson's correlation and the intraclass correlation coefficients for the contextual factor from each perspective and compared the ranking of the 10 contextual factors with the highest abilities. RESULTS: Seven hundred and ninety-three patients' and 795 physicians' perspectives estimated the ability (i.e., importance) of the contextual factors in 11 963 paired comparisons. We found a high correlation between physicians' and patients' perspectives of the contextual factors to be considered for smoking cessation (r = 0.76, P < 0.0001). However, the agreement between the abilities of contextual factors was poor (ICC = 0.42 [-0.10; 0.75]; P = 0.09). Fine-grain analysis of participants' answers revealed many discrepancies. For example, 40% factors ranked in the top 10 most important for physicians were not in patients' top 10 ranking. CONCLUSION: Our results highlight the importance of patient-centered care, the need to engage discussions about patients' values, beyond what is thought to be important, to avoid overlooking their real context.

Pharmacological Treatment of Fibromyalgia Syndrome: A Practice-Based Review.

PURPOSE OF REVIEW: Fibromyalgia Syndrome (FMS) is a complex chronic pain condition characterized by widespread musculoskeletal pain and numerous other debilitating symptoms. The purpose of this review is to provide a comprehensive overview, based on everyday clinical practice, of the drugs presently employed in the treatment of FMS. RECENT FINDINGS: The treatment of FMS is based on a multimodal approach, with pharmacologic treatment being an essential pillar. The drugs used include tricyclic antidepressants, serotonin and noradrenaline reuptake inhibitors, other antidepressants, anticonvulsants, myorelaxants, and analgesics. The effectiveness of these medications varies, and the choice of drug often depends on the specific symptoms presented by the patient. Many drugs tend to either address only some domains of the complex FMS symptomatology or have a limited effect on pain. Each treatment option comes with potential side effects and risks that necessitate careful consideration. It may be beneficial to divide patients into clinical subpopulations, such as FMS with comorbid depression, for more effective treatment. Despite the complexities and challenges, the pharmacological treatment remains a crucial part for the management of FMS. This review aims to guide clinicians in prescribing pharmacological treatment to individuals with FMS.

Treatment Options for Posttraumatic Headache: A Current Review of the Literature.

PURPOSE OF REVIEW: We evaluate evidence-based treatments for posttraumatic headache (PTH), a secondary headache disorder resulting from traumatic brain injury (TBI), comprising nearly 4% of all symptomatic headache disorders. Utilizing recent publications, we aim to inform clinicians of current treatment methods. RECENT FINDINGS: There is limited research on PTH treatment. A randomized controlled trial (RCT) of metoclopramide with diphenhydramine for acute PTH found that the treatment group (N = 81) experienced more significant pain improvement than placebo by 1.4 points. For persistent PTH, an open-label study of erenumab (N = 89) found that 28% of participants reported ≥ 50% reduction in moderate-to-severe headache days, but an RCT of fremanezumab showed a non-significant reduction in moderate-to-severe headache days. A randomized crossover study of 40 patients with persistent PTH found that onabotulinum toxin-A decreased cumulative number of headaches/week by 43.3% in the treatment group and increased by 35.1% among placebos. In a study of military veterans with severe posttraumatic stress disorder and persistent/delayed onset PTH (N = 193), patients who received Cognitive Behavioral Therapy reported significant improvements in headache-related disability compared to usual care (aggregate mean HIT-6, -3.4). A transcranial magnetic stimulation (N = 24) study found that 58% of participants with mild TBI-related headache experienced a 50% reduction in headache frequency. New studies indicate promise in improving clinically important outcomes of PTH. However, more research is necessary to determine the optimal treatment and whether combining pharmacologic and nonpharmacologic treatment versus a single modality is more effective.

Levonorgestrel intrauterine system versus dienogest effect on quality of life of women with deep endometriosis: a randomized open-label clinical trial.

Women with deep infiltrating endometriosis (DIE) can benefit from the use of progestins. Our aim is to explore if levonorgestrel-releasing intrauterine system (LNG-IUS) non inferior to dienogest (DNG) in improving deep endometriosis women's quality of life (QoL). This randomized open-label clinical trial included forty women with DIE assessed using clinical history and physical examination, transvaginal ultrasonography and magnetic resonance of the pelvis without any previous surgical treatment, with two treatments arms. The two groups underwent a 3-month washout of hormonal treatments, and then received either DNG or LNG-IUS for 6 months. QoL was assessed prior to and 6 months after the intervention, using the SF36 and the EHP30. DNG and LNG-IUS showed an increase on all domains of the SF36 (p < .001). There was no difference between treatments on the improvement observed (p > .05 for all domains). DNG and LNG-IUS, also, showed improvement on all domains of EHP30 (p < .001), except "relationship with children" and "feelings about pregnancy." However, there was no statistical difference between treatments for all sections scores (p > .05). The treatment of deep endometriosis symptoms using either DNG or LNG-IUS in women with no prior surgical treatment is associated with improvement in QoL.Trial Registration Number: This trial is registered on "The Brazilian Registry of Clinical Trials (ReBECID: RBR-8fjx2jp)," that is part of Primary Registries in the WHO Registry Network, under the title: "Dienogest versus Levonorgestrel IUS on deep endometriosis patient´s QoL without surgery" on June 14, 2021; https://ensaiosclinicos.gov.br/rg/RBR-8fjx2jp.

Cognitive training for children with ADHD: composite cognitive score outcome in a randomized controlled trial.

PURPOSE OF THE ARTICLE: Cognitive training for Attention Deficit/Hyperactivity Disorder (ADHD) has shown promising, although mixed results. In post-hoc analyses, we evaluate effects of cognitive training using a novel composite cognition score as the outcome for children attending at least 16 sessions of training, dose-response of training and associations between symptoms and cognitive functioning. MATERIALS AND METHODS: Children (age 6-13) with ADHD were randomized to intervention (n = 26) or control (n = 34). For the current analysis, we restricted the intervention group to children, who completed at least 16 sessions of cognitive training (n = 26) and examined a dose response within that group. RESULTS: Cognition improved significantly in the intervention, but not control group. Amount of the completed training sessions correlated significantly with the amount of cognitive improvement. CONCLUSION: Variations in dose and frequency of training may be an important source of the variance in previous studies.

Pharmacological therapy in the management of temporomandibular disorders and orofacial pain: a systematic review and meta-analysis.

BACKGROUND: Temporomandibular disorders (TMD) are manifested by soreness in the jaw joint area and jaw muscles, clicks or creaks when opening or closing the mouth. All these symptoms can be disabling and occur during chewing and when the patient yawns or speaks. Several classes of drugs are used to treat symptoms. This review aims to assess which drug suits the different signs. METHODS: Pubmed, Web of Science and Lilacs were systematically searched until 01/02/2023. Clinical trials were selected that dealt with drugs used in temporomandibular dysfunction RESULTS: Out of 830 papers, eight studies were included. The Meta-Analysis with Continuous Outcomes with Pre-Calculated Effect Sizes resulted in the rejection that there is intergroup variability (p.0.74). CONCLUSIONS: Treatment of orofacial pain is still a significant challenge for dentistry. We can conclude that there is no drug of first choice in the treatment of temporomandibular pain. However, the clinician must distinguish the type of pain and the aetioloic cause of the pain so that the patient can be treated and managed pharmacologically.

[Pharmacological treatment of obesity. Current situation and new treatments]. / Tratamiento farmacológico de la obesidad. Situación actual y nuevos tratamientos.

The high incidence of obesity in our environment, the progressive and recurrent nature of this disease makes it necessary to know and use all the possibilities of prevention and treatment. When a person suffers from obesity we must offer a treatment plan with specific objectives that will include healthy eating, physical activity and, if necessary, treatment with medication or even surgery. At present in Spain, there are 3 medications available: New molecules will soon be marketed that will expand the treatment possibilities, which will also be reviewed in this article.

The treatment of behavioural and psychological symptoms in dementia: pragmatic recommendations.

Behavioural and psychological symptoms of dementia (BPSD) are a clinical challenge for the lack of a sound taxonomy, frequent presentation with comorbid BPSD, lack of specific pharmacologic interventions, poor base of methodologically sound evidence with randomized clinical trials, contamination from the treatment of behavioural disturbances of young and adult psychiatric conditions, and small efficacy window of psychotropic drugs. We present here a treatment workflow based on a concept-driven literature review based on the notions that (i) the aetiology of BPSD can be mainly neurobiological (so-called 'primary' symptoms) or mainly environmental and functional ('secondary' symptoms) and that this drives treatment; (ii) the clinical efficacy of psychotropic drugs is driven by their specific profile of receptor affinity; (iii) drug treatment should follow the rules of 'start low-go slow, prescribe and revise'. This article argues in support of the distinction between primary and secondary BPSD, as well as their characteristics, which until now have been just sketchily described in the literature. It also offers comprehensive and pragmatic clinician-oriented recommendations for the treatment of BPSD.

11. Cervicogenic headache and occipital neuralgia.

INTRODUCTION: Cervicogenic headache (CEH) and occipital neuralgia (ON) are headaches originating in the occiput and that radiate to the vertex. Because of the intimate relationship between structures based in the occiput and those in the upper cervical region, there is significant overlap between the presentation of CEH and ON. Diagnosis starts with a headache history to assess for diagnostic criteria formulated by the International Headache Society. Physical examination evaluates range of motion of the neck and the presence of tender areas or pressure points. METHODS: The literature for the diagnosis and treatment of CEH and ON was searched from 2015 through August 2022, retrieved, and summarized. RESULTS: Conservative treatment includes pain education and self-care, analgesic medication, physical therapy (such as reducing secondary muscle tension and improving posture), the use of TENS (transcutaneous electrical nerve stimulation), or a combination of the aforementioned treatments. Injection at various anatomical locations with local anesthetic with or without corticosteroids can provide pain relief for a short period. Deep cervical plexus block can result in improved pain for less than 6 months. In both CEH and ON, an occipital nerve block can provide important diagnostic information and improve pain in some patients, with PRF providing greater long-term pain control. Radiofrequency ablation of the cervical facet joints can result in improvement for over 1 year. Occipital nerve stimulation (ONS) should be considered for the treatment of refractory ON. CONCLUSION: The treatment of CEH preferentially consists of radiofrequency treatment of the facet joints, while for ON, pulsed radiofrequency of the occipital nerves is indicated. For refractory cases, ONS may be considered.

Management of Potential Organ Donor: Indian Society of Critical Care Medicine-Position Statement.

This position statement is documented based on the input from all contributing coauthors from the Indian Society of Critical Care Medicine (ISCCM), following a comprehensive literature review and summary of current scientific evidence. Its objective is to provide the standard perspective for the management of potential organ/tissue donors after brain death (BD) in adults only, regardless of the availability of technology. This document should only be used for guidance only and is not a substitute for proper clinical decision making in particular circumstances of any case. Endorsement by the ISCCM does not imply that the statements given in the document are applicable in all or in a particular case; however, they may provide guidance for the users thus facilitating maximum organ availability from brain-dead patients. Thus, the care of potential brain-dead organ donors is "caring for multiple recipients." How to cite this article: Zirpe K, Pandit R, Gurav S, Mani RK, Prabhakar H, Clerk A, et al. Management of Potential Organ Donor: Indian Society of Critical Care Medicine-Position Statement. Indian J Crit Care Med 2024;28(S2):S249-278.

Presence of depression and anxiety with distinct patterns of pharmacological treatments before the diagnosis of chronic fatigue syndrome: a population-based study in Taiwan.

OBJECTIVE: An increased prevalence of psychiatric comorbidities (including depression and anxiety disorder) has been observed among patients with chronic fatigue syndrome (CFS). However, few studies have examined the presence of depression and anxiety disorder before the diagnosis of CFS. This study aimed to clarify the preexisting comorbidities and treatments associated with patients with subsequent CFS diagnosis in a population-based cohort in Taiwan. METHODS: An analysis utilizing the National Health Insurance Research Database of Taiwan was conducted. Participants included were 6303 patients with CFS newly diagnosed between 2000 and 2010 and 6303 age-/sex-matched controls. RESULTS: Compared with the control group, the CFS group had a higher prevalence of depression and anxiety disorder before the diagnosis of CFS. Sampled patients who took specific types of antidepressants, namely, selective serotonin reuptake inhibitors (adjusted odds ratio [aOR] = 1.21, 95% confidence interval [CI] 1.04-1.39), serotonin antagonists and reuptake inhibitors (SARI; aOR = 1.87, 95% CI 1.59-2.19), and tricyclic antidepressants (aOR = 1.46, 95% CI 1.09-1.95), had an increased risk of CFS. CFS risk was also higher among participants taking benzodiazepine, muscle relaxants, and analgesic drugs. A sub-group analysis revealed that SARI use was related to an increased risk of CFS in the depression, anxiety disorder, male, and female groups. In the depression and anxiety disorder groups, analgesic drug use was associated with an increased CFS risk. Nonpharmacological treatment administration differed between men and women. CONCLUSION: This population-based retrospective cohort study revealed an increased risk of CFS among populations with preexisting depression and anxiety disorder, especially those taking SARI and analgesic drugs.

Quality of life in sarcoidosis.

Having sarcoidosis often has a major impact on quality of life of patients and their families. Improving quality of life is prioritized as most important treatment aim by many patients with sarcoidosis, but current evidence and treatment options are limited. In this narrative review, we describe the impact of sarcoidosis on various aspects of daily life, evaluate determinants of health-related quality of life (HRQoL), and provide an overview of the different patient-reported outcome measures to assess HRQoL in sarcoidosis. Moreover, we review the current evidence for pharmacological and non-pharmacological interventions to improve quality of life for people with sarcoidosis.

Pharmacological inhibition of SK-channels with AP14145 prevents atrial arrhythmogenic changes in a porcine model for obstructive respiratory events.

BACKGROUND: Obstructive sleep apnea (OSA) creates a complex substrate for atrial fibrillation (AF), which is refractory to many clinically available pharmacological interventions. We investigated atrial antiarrhythmogenic properties and ventricular electrophysiological safety of small-conductance Ca2+ -activated K+ (SK)-channel inhibition in a porcine model for obstructive respiratory events. METHODS: In spontaneously breathing pigs, obstructive respiratory events were simulated by intermittent negative upper airway pressure (INAP) applied via a pressure device connected to the intubation tube. INAP was applied for 75 s, every 10 min, three times before and three times during infusion of the SK-channel inhibitor AP14145. Atrial effective refractory periods (AERP) were acquired before (pre-INAP), during (INAP) and after (post-) INAP. AF-inducibility was determined by a S1S2 atrial pacing protocol. Ventricular arrhythmicity was evaluated by heart rate adjusted QT-interval duration (QT-paced) and electromechanical window (EMW) shortening. RESULTS: During vehicle infusion, INAP transiently shortened AERP (pre-INAP: 135 ± 10 ms vs. post-INAP 101 ± 11 ms; p = .008) and increased AF-inducibility. QT-paced prolonged during INAP (pre-INAP 270 ± 7 ms vs. INAP 275 ± 7 ms; p = .04) and EMW shortened progressively throughout INAP and post-INAP (pre-INAP 80 ± 4 ms; INAP 59 ± 6 ms, post-INAP 46 ± 10 ms). AP14145 prolonged baseline AERP, partially prevented INAP-induced AERP-shortening and reduced AF-susceptibility. AP14145 did not alter QT-paced at baseline (pre-AP14145 270 ± 7 ms vs. AP14145 268 ± 6 ms, p = .83) or QT-paced and EMW-shortening during INAP. CONCLUSION: In a pig model for obstructive respiratory events, the SK-channel-inhibitor AP14145 prevented INAP-associated AERP-shortening and AF-susceptibility without impairing ventricular electrophysiology. Whether SK-channels represent a target for OSA-related AF in humans warrants further study.