Stroke outcomes following durable left ventricular assist device implant in patients bridged with micro-axial flow pump: Insights from a large registry.

BACKGROUND: Stroke after durable left ventricular assist device (d-LVAD) implantation portends high mortality. The incidence of ischemic and hemorrhagic stroke and the impact on stroke outcomes of temporary mechanical circulatory support (tMCS) management among patients requiring bridge to d-LVAD with micro-axial flow-pump (mAFP, Abiomed) is unsettled. METHODS: Consecutive patients, who underwent d-LVAD implantation after being bridged with mAFP at 19 institutions, were retrospectively included. The incidence of early ischemic and hemorrhagic stroke after d-LVAD implantation (<60 days) and association of pre-d-LVAD characteristics and peri-procedural management with a specific focus on tMCS strategies were studied. RESULTS: Among 341 patients, who underwent d-LVAD implantation after mAFP implantation (male gender 83.6%, age 58 [48-65] years, mAFP 5.0/5.5 72.4%), the early ischemic stroke incidence was 10.8% and early hemorrhagic stroke 2.9%. The tMCS characteristics (type of mAFP device and access, support duration, upgrade from intra-aortic balloon pump, ECMELLA, ECMELLA at d-LVAD implantation, hemolysis, and bleeding) were not associated with ischemic stroke after d-LVAD implant. Conversely, the device model (mAFP 2.5/CP vs. mAFP 5.0/5.5: HR 5.6, 95%CI 1.4-22.7, p = 0.015), hemolysis on mAFP support (HR 10.5, 95% CI 1.3-85.3, p = 0.028) and ECMELLA at d-LVAD implantation (HR 5.0, 95% CI 1.4-18.7, p = 0.016) were associated with increased risk of hemorrhagic stroke after d-LVAD implantation. Both early ischemic (HR 2.7, 95% CI 1.9-4.5, p < 0.001) and hemorrhagic (HR 3.43, 95% CI 1.49-7.88, p = 0.004) stroke were associated with increased 1-year mortality. CONCLUSIONS: Among patients undergoing d-LVAD implantation following mAFP support, tMCS characteristics do not impact ischemic stroke occurrence, while several factors are associated with hemorrhagic stroke suggesting a proactive treatment target to reduce this complication.

A Female-Specific Treatment Group for ADHD-Description of the Programme and Qualitative Analysis of First Experiences.

Background: The diagnostics and treatment of attention-deficit/hyperactivity disorder (ADHD) in women remain insufficient. Fluctuations of reproductive hormones during the premenstrual period, postpartum period, and (peri)menopause are neglected, even though they impact ADHD symptoms and associated mood disorders. Therefore, we created a female-specific treatment group for women with ADHD and premenstrual worsening of ADHD and/or mood symptoms. Methods: We describe the group programme and underlying rationale, offering a qualitative analysis of the participants' evaluation. Results: The seven bi-weekly sessions foreground the menstrual cycle and address several ADHD-specific topics in relation to this cyclical pattern. Concurrently, women track their menstrual cycle and (fluctuating) ADHD and mood symptoms with an adjusted premenstrual calendar. In total, 18 women (25-47 years) participated in three consecutive groups. We analysed the evaluation of the last group. Participants experienced the group as a safe and welcoming space. Recognition was valued by all. The topics discussed were deemed valuable, and the structure suited them well. Completing the premenstrual calendar augmented the awareness and recognition of individual cyclical symptoms. A lifespan approach increased self-understanding. Participants took their menstrual cycle more seriously, prioritising self-acceptance and self-care. Conclusions: Exploring a cyclical approach in a group setting seems to be a positive addition to treatment for female ADHD.

Female-specific pharmacotherapy in ADHD: premenstrual adjustment of psychostimulant dosage.

Objective: Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental condition which is underdiagnosed and undertreated in women. For decades, the ADHD field has called for more insight into female-specific therapy. Preliminary findings postulate that changes in sex hormones during the menstrual cycle may influence the effectiveness of psychostimulant medication. Yet, pharmacotherapeutic interventions tailored to women with ADHD remain scarce. Previously, our group showed an increase in mood symptoms in the premenstrual week in women with ADHD. Premenstrual worsening of depressive and ADHD symptoms represent a treatment challenge. In our adult ADHD clinic, we noted several women describing exacerbation of their ADHD and depressive symptoms in the premenstrual week and/or insufficient effect of their established dosage of psychostimulant. We responded to the need expressed by these women by increasing their stimulant dosage in the premenstrual week, while monitoring the response and side effects. Methods: This community case study of nine consecutive women being treated for ADHD and co-occurring conditions (including depression and premenstrual dysphoric disorder), reports our local experience of increasing the individually prescribed psychostimulant dosage during the premenstrual period. We methodically monitored the effect of this increased dosage on ADHD symptoms, mood and somatic symptoms for the following 6-24 months. Results: With premenstrual dose elevation, all nine women experienced improved ADHD and mood symptoms with minimal adverse events. Premenstrual inattention, irritability and energy levels improved, and now resembled the other non-premenstrual weeks more closely. All women decided to continue with the elevated premenstrual pharmacotherapy. Discussion: Our preliminary results demonstrate potential benefits of increasing premenstrual psychostimulant dosage in women with ADHD, experiencing premenstrual worsening of ADHD and mood symptoms. The results concur with previous findings of diminished response to amphetamines in the late luteal phase. Increased dosage may help combat premenstrual worsening of cognitive and emotional symptoms in women with ADHD, with significant clinical implications. Better management of premenstrual ADHD and mood symptoms in vulnerable women can improve treatment outcome and meet an unmet need. However, implementation should be individually explored. Further investigation of luteal phase psychostimulant dose adjustment is required for safe, optimal and individualised treatment for women with ADHD.

Cardiovascular risk in adults with Delayed Sleep Phase Syndrome (DSPS) and Attention-Deficit/Hyperactivity Disorder (ADHD).

TRIAL REGISTRATION: FASE, https://www.trialregister.nl/, #NTR3831.

Treatment of 95 post-Covid patients with SSRIs.

After Covid-19 infection, 12.5% develops post-Covid-syndrome (PCS). Symptoms indicate numerous affected organ systems. After a year, chronic fatigue, dysautonomia and neurological and neuropsychiatric complaints predominate. In this study, 95 PCS patients were treated with selective serotonin reuptake inhibitors (SSRIs). This study used an exploratory questionnaire and found that two-thirds of patients had a reasonably good to strong response on SSRIs, over a quarter of patients had moderate response, while 10% reported no response. Overall, patients experienced substantial improved well-being. Brainfog and sensory overload decreased most, followed by chronic fatigue and dysautonomia. Outcomes were measured with three different measures that correlated strongly with each other. The response to SSRIs in PCS conditions was explained by seven possible neurobiological mechanisms based on recent literature on PCS integrated with already existing knowledge. Important for understanding these mechanisms is the underlying biochemical interaction between various neurotransmitter systems and parts of the immune system, and their dysregulation in PCS. The main link appears to be with the metabolic kynurenine pathway (KP) which interacts extensively with the immune system. The KP uses the same precursor as serotonin: tryptophan. The KP is overactive in PCS which maintains inflammation and which causes a lack of tryptophan. Finally, potential avenues for future research to advance this line of clinical research are discussed.

Lifetime ADHD symptoms highly prevalent in women with cardiovascular complaints. A cross-sectional study.

Patients with Attention Deficit Hyperactivity Disorder (ADHD) are at greater cardiovascular risk. We investigated the association between ADHD symptoms and cardiovascular disease in women at a specialized Dutch cardiological clinic. Lifetime ADHD symptoms were found in 35% of women (n = 300) with cardiac complaints. Women with ADHD symptoms compared to those without were significantly younger but had no different cardiological profile. To protect women's health, further research and multidisciplinary cooperation is required to better understand the relationship between ADHD and cardiovascular disease.

Attention-Deficit/Hyperactivity Disorder and Delayed Sleep Phase Syndrome in Adults: A Randomized Clinical Trial on the Effects of Chronotherapy on Sleep.

Delayed sleep phase syndrome (DSPS) is the most common sleep disturbance in adults with attention-deficit/hyperactivity disorder (ADHD). We previously showed that chronotherapy with melatonin effectively advanced the dim-light melatonin onset (DLMO), a biomarker for the internal circadian rhythm, by 1.5 h and reduced ADHD symptoms by 14%. Melatonin combined with bright light therapy (BLT) advanced the DLMO by 2 h, but did not affect ADHD symptoms. This article explores whether sleep times advanced along with DLMO, leading to longer sleep duration and better sleep in general, which might explain the working mechanism behind the reduction in ADHD symptoms after treatment with melatonin. This article presents exploratory secondary analysis on objective and self-reported sleep characteristics from a three-armed double-blind randomized placebo-controlled clinical trial (RCT), which included 49 adults (18-55 years) with ADHD and DSPS. Participants were randomized to receive sleep education and 3 weeks of (1) 0.5 mg/day placebo, (2) 0.5 mg/day melatonin, or (3) 0.5 mg/day melatonin plus 30 min of bright light therapy (BLT) between 0700 and 0800 h. Sleep was assessed at baseline, directly after treatment, and 2 weeks after the end of treatment. Objective measures were obtained by actigraphy, self-reported measures by various sleep questionnaires and a sleep diary. Melatonin with or without BLT did not advance sleep times, improve sleep in general, or strengthen wake-activity rhythms. So even though the DLMO had advanced, sleep timing did not follow. Adding extensive behavioral coaching to chronotherapy is necessary for advancing sleep times along with DLMO and to further alleviate ADHD symptoms.

Combined impact of ADHD and insomnia symptoms on quality of life, productivity, and health care use in the general population.

BACKGROUND: Both attention-deficit/hyperactivity disorder (ADHD) and insomnia have been independently related to poorer quality of life (QoL), productivity loss, and increased health care use, although most previous studies did not take the many possible comorbidities into account. Moreover, ADHD and insomnia often co-occur. Symptoms of ADHD and insomnia together may have even stronger negative effects than they do separately. We investigated the combined effects of symptoms of ADHD and insomnia, in addition to their independent effects, on QoL, productivity, and health care use, thereby controlling for a wide range of possible comorbidities and confounders. METHODS: Data from the third wave of the Netherlands Mental Health Survey and Incidence Study-2 were used, involving N = 4618 from the general population. Both the inattention and the hyperactivity ADHD symptom dimensions were studied, assessed by the ASRS Screener. RESULTS: Mental functioning and productivity were negatively associated with the co-occurrence of ADHD and insomnia symptoms, even after adjusting for comorbidity and confounders. The results show no indication of differences between inattention and hyperactivity. Poorer physical functioning and health care use were not directly influenced by the interaction between ADHD and insomnia. CONCLUSIONS: People with both ADHD and sleep problems have increased risk for poorer mental functioning and productivity loss. These results underscore the importance of screening for sleep problems when ADHD symptoms are present, and vice versa, and to target both disorders during treatment.

Review: Identification and Management of Circadian Rhythm Sleep Disorders as a Transdiagnostic Feature in Child and Adolescent Psychiatry.

OBJECTIVE: Sleep disturbances are highly frequent features in a range of child and adolescent psychiatric conditions. However, it is commonly not clear if such sleep problems represent symptomatic features of, comorbidities of, or risk factors for these conditions. It is believed that underlying dysfunction in the daily biological (circadian) clock may play important roles in the etiology of many sleep disorders, and circadian rhythm changes are reported in a number of neuropsychiatric conditions. The aim of this review was to explore the key identifying features of circadian rhythm disorders (CRDs) in child and adolescent psychiatry and address how such disorders may be managed in the clinic. METHOD: A narrative review was conducted of the extant literature of CRDs in children and adolescents with psychiatric conditions. RESULTS: Key biological and social factors that contribute to CRDs in children and adolescents, and the cognitive and neurobehavioral consequences resulting from insufficient sleep were outlined. The roles of melatonin and other chronotherapeutic and behavioral interventions for the management of CRDs were also outlined. Further, the importance of careful investigation of circadian rhythm abnormalities in shaping the most effective treatment plan according to chronobiological principles was highlighted. CONCLUSION: CRDs are common in children and adolescents with psychiatric conditions and arise out of complex interactions between biological and social factors. Careful clinical attention to and management of CRDs in child and adolescent psychiatry have the potential for significant benefit not only in the domain of sleep but also in a range of cognitive, affective, and behavioral outcomes.

The World Federation of ADHD International Consensus Statement: 208 Evidence-based conclusions about the disorder.

BACKGROUND: Misconceptions about ADHD stigmatize affected people, reduce credibility of providers, and prevent/delay treatment. To challenge misconceptions, we curated findings with strong evidence base. METHODS: We reviewed studies with more than 2000 participants or meta-analyses from five or more studies or 2000 or more participants. We excluded meta-analyses that did not assess publication bias, except for meta-analyses of prevalence. For network meta-analyses we required comparison adjusted funnel plots. We excluded treatment studies with waiting-list or treatment as usual controls. From this literature, we extracted evidence-based assertions about the disorder. RESULTS: We generated 208 empirically supported statements about ADHD. The status of the included statements as empirically supported is approved by 80 authors from 27 countries and 6 continents. The contents of the manuscript are endorsed by 366 people who have read this document and agree with its contents. CONCLUSIONS: Many findings in ADHD are supported by meta-analysis. These allow for firm statements about the nature, course, outcome causes, and treatments for disorders that are useful for reducing misconceptions and stigma.

Reliability, Criterion and Concurrent Validity of the Farsi Translation of DIVA-5: A Semi-Structured Diagnostic Interview for Adults With ADHD.

Objectives: This study evaluated the psychometrics of the Farsi translation of diagnostic interview for attention-deficit hyperactivity disorder (ADHD) in adults (DIVA-5) based on DSM-5 criteria. Methods: Referrals to a psychiatric outpatient clinic (N = 120, 61.7% males, mean age 34.35 ± 9.84 years) presenting for an adult ADHD (AADHD) diagnosis, were evaluated using the structured clinical interviews for DSM-5 (SCID-5 & SCID-5-PD) and the DIVA-5. The participants completed Conner's Adult ADHD Rating Scale-Self Report-Screening Version (CAARS-S-SV). Results: According to the SCID-5 and DIVA-5 diagnoses, 55% and 38% of the participants had ADHD, respectively. Diagnostic agreement was 81.66% between DIVA-5/SCID-5 diagnoses, 80% between SCID-5/CAARS-S-SV, and 71.66% between DIVA-5/CAARS-S-SV. Test-retest and inter-rater reliability results for the DIVA-5 were good to excellent. Conclusion: Findings support the validity and reliability of the Farsi translation of DIVA-5 among the Farsi-speaking adult outpatient population.

Response and Side Effects Using Stimulant Medication in Older Adults With ADHD: An Observational Archive Study.

Objective: To examine the naturalistic response to and cardiovascular side effects of stimulant medication in older adults with ADHD. Methods: Electronic Health Record (EHR) data of adult patients with ADHD (≥55 years) at the specialized PsyQ outpatient clinic for adult ADHD (n = 113, 55-79 years) were collected. Response, cardiovascular status, side effects, and provided medical care before and after the first ADHD medication dose have been recorded. Results: A total of 65% of the patients reported positive response to the medication, and 42% of the patients quit their medication due to side effects or nonresponse. There was a small but significant decrease in weight and increase in heart rate before and after methylphenidate use. Conclusion: Our results indicate that the use of stimulants may be a relatively safe and effective treatment for older adults with ADHD, under the condition that the cardiovascular parameters are monitored before and during pharmacological treatment. Randomized controlled trials (RCTs) are needed to confirm these findings.

Prevalence of hormone-related mood disorder symptoms in women with ADHD.

This is the first study to assess the prevalence of symptoms of premenstrual dysphoric disorder (PMDD), episodes of postpartum depression symptoms (PPD) after first childbirth, and climacteric mood symptoms in Attention-Deficit/Hyperactivity Disorder (ADHD). 209 consecutive women (18-71 years) with ADHD completed the PMDD chapter of the Neuropsychiatric Interview Plus version 5.0.0 to assess PMDD, the Edinburgh Postnatal Depression Scale to assess PPD, and the Greene Climacteric Scale to assess climacteric symptoms. Comorbid psychiatric disorders, medication use, and chronobiological sleep characteristics were also assessed. The prevalence of PMDD and PPD were high in ADHD, compared to the general population. PMDD symptoms were associated with less use of contraceptives. Antidepressants were associated with more PMDD symptoms. The following GCS scores were significant increased: anxiety, depression, and sexual dysfunction, vasomotor and somatic complaints. No significant differences were found in sleep characteristics or current comorbidity between the groups with and without PPD or PMDD, or increased climacteric scores. The prevalences of PMDD, PPD and climacteric scores were high in women with ADHD. This is the first study in women with ADHD that suggests that female ADHD patients suffer from significant PMDD symptoms, experience PPD during the first child birth, and experience more severe climacteric symptoms.

Effects of chronotherapy on circadian rhythm and ADHD symptoms in adults with attention-deficit/hyperactivity disorder and delayed sleep phase syndrome: a randomized clinical trial.

The majority of adults with Attention-Deficit/Hyperactivity Disorder (ADHD) have a delayed circadian rhythm that is a characteristic of Delayed Sleep Phase Syndrome (DSPS). Treatment of DSPS may improve both the circadian rhythm and ADHD symptoms. In this three-armed randomized clinical trial, 51 adults (18-55 y) with ADHD and DSPS received sleep education and 3 weeks of (1) 0.5 mg/d placebo, (2) 0.5 mg/d melatonin, or (3) 0.5 mg/d melatonin plus 30 minutes of 10,000 lux bright light therapy (BLT) between 07:00 and 08:00 h. Placebo/melatonin conditions were double-blind. Treatment took place in the participants' naturalistic home settings. Dim-light melatonin onset (DLMO) was measured in saliva as marker of internal circadian rhythm. Melatonin or placebo administration followed individual schedules, starting 3 hours before the individual DLMO and weekly advancing by 1 h. DLMO and ADHD Rating Scale score were assessed at baseline, directly after 3-week treatment, and two weeks after the end of treatment. Results show that at baseline 77% had a DLMO after 21:00 h with an average DLMO at 23:43 h ± 1h46. Directly after treatment, melatonin had advanced DLMO by 1h28 (p = .001), and melatonin plus BLT by 1h58 (p < .001). Placebo did not affect DLMO. ADHD symptoms reduced by 14% (p = .038) directly after melatonin treatment. Placebo and melatonin plus BLT did not impact ADHD symptoms. Two weeks after end of treatment, ADHD symptoms and DLMO had returned to baseline levels. It can be concluded that low doses of melatonin advanced the circadian rhythm and reduced self-reported ADHD symptoms. Given the large number of adult ADHD patients with concurrent DSPS, treating delayed sleep with melatonin is an important component of effective ADHD treatment.

Effects of prolonged methylphenidate treatment on amygdala reactivity and connectivity: a randomized controlled trial in stimulant treatment-naive, male participants with ADHD.

Background: Problems with emotional processing are widely reported in individuals with attention-deficit/hyperactivity disorder (ADHD). Although methylphenidate (MPH) effectively alleviates inattention and hyperactivity symptoms in ADHD, its effects on emotional processing and internalizing symptoms have remained elusive. While we previously found that acute MPH administration modulated neural mechanisms underlying emotional processing in an age-dependent manner, the effects of prolonged administration remained unknown. Objectives: Therefore, we investigated: (i) whether prolonged MPH treatment influences neural substrates (amygdala reactivity and connectivity) of emotional processing, and (ii) whether these effects are modulated by age. Methods: The "effects of Psychotropic drugs On Developing brain-MPH" ("ePOD-MPH") randomized controlled trial was a 16-week double-blind, placebo-controlled, multi-center trial with MPH in 50 boys (10-12 years of age) and 49 men (23-40 years of age), all stimulant treatment-naive and diagnosed with ADHD. Participants performed an emotional face-matching task during functional magnetic resonance imaging. We assessed their symptoms of ADHD and internalizing symptoms at baseline, during the trial (8 weeks), and 1 week after the trial end (17 weeks). Results and Conclusions: We did not find effects of prolonged MPH treatment on emotional processing, as measured by amygdala reactivity and connectivity and internalizing symptoms in this trial with stimulant treatment-naive participants. This differs from our findings on emotional processing following acute MPH administration and the effects of prolonged MPH treatment on the dopamine system, which were both modulated by age. Interestingly, prolonged MPH treatment did improve ADHD symptoms, although depressive and anxiety symptoms showed a medication-independent decrease. Furthermore, our data indicate that baseline internalizing symptoms may be used to predict MPH treatment effects on ADHD symptoms, particularly in (male) adults with ADHD.

Validity of the Korean Version of DIVA-5: A Semi-Structured Diagnostic Interview for Adult ADHD.

BACKGROUND: This study was to assess the validity of the Korean version of the semi-structured Diagnostic Interview for Adult ADHD, third edition (DIVA-5). The secondary aim was to compare sociodemographic and psychiatric comorbidities in adult patients with and without a diagnosis of ADHD. METHODS: A total of 279 participants were recruited from nine psychiatric outpatient clinics in Korea. All participants were administered the Mini-International Neuropsychiatric Interview (MINI) Plus v.5.0.0, the Adult ADHD Self-Report Scale v1.1 (ASRS-v1.1) Symptom Checklist, and DIVA-5. Diagnosis concordance between two board-certified psychiatrists and DIVA-5 were analysed. RESULTS: The DIVA-5 showed a diagnostic accuracy of 92%, a sensitivity of 91.30%, and a specificity of 93.62%. Significant clinical and demographic differences between ADHD and control groups were found. CONCLUSION: The Korean version of DIVA-5 is a reliable tool for assessing and diagnosing ADHD in adult Korean populations.

[Risk of psychosis with treatment for ADHD]. / Kans op psychose bij behandeling van ADHD.

The study by Moran et al. on the risk of psychosis among adolescents in the US who are treated with a stimulant for ADHD is important. This is because ADHD is a common disorder (3-5%), because psychosis often emerges in adolescence, because ADHD and psychosis share increased comorbidity and because ADHD is treated with stimulant medication that may increase the risk of psychosis. This means there is a multifactorial relationship between ADHD and psychosis.The outcome of the study is that stimulants increase the risk of psychosis to a limited extent, i.e. 0.10% for methylphenidate and 0.21% for dexamphetamine. It is recommended to opt for methylphenidate in adolescents with ADHD. This is confirmed by a Swedish registry study that controlled for a history of psychosis and showed that methylphenidate did not increase the incidence of psychosis after one year, regardless of a history of psychosis.

Delayed sleep-onset and biological age: late sleep-onset is associated with shorter telomere length.

STUDY OBJECTIVES: We evaluated the relationship between leukocyte telomere length (LTL) and sleep duration, insomnia symptoms, and circadian rhythm, to test whether sleep and chronobiological dysregulations are associated with cellular aging. METHODS: Data from the Netherlands Study of Depression and Anxiety (N = 2,936) were used at two waves 6 years apart, to measure LTL. Telomeres shorten during the life span and are important biomarkers for cellular aging. LTL was assessed by qualitative polymerase chain reaction and converted into base pair number. Sleep parameters were: sleep duration and insomnia symptoms from the Insomnia Rating Scale. Circadian rhythm variables were: indication of Delayed Sleep Phase Syndrome (DSPS), mid-sleep corrected for sleep debt on free days (MSFsc), sleep-onset time, and self-reported chronotype, from the Munich Chronotype Questionnaire. Generalized estimating equations analyzed the associations between LTL, sleep, and chronobiological factors, adjusted for baseline age, sex, North European ancestry, and additionally for current smoking, depression severity, obesity, and childhood trauma. RESULTS: Indicators of delayed circadian rhythm showed a strong and consistent effect on LTL, after adjustment for sociodemographic and health indicators. Late MSFsc (B = -49.9, p = .004), late sleep-onset time (B = -32.4, p = .001), indication of DSPS (B = -73.8, p = .036), and moderately late chronotype in adulthood (B = -71.6, p = .003) were associated with significantly shorter LTL across both waves; whereas sleep duration and insomnia symptoms were not. Extremely early chronotype showed significantly less LTL shortening than intermediate chronotype (B = 161.40, p = .037). No predictors showed accelerated LTL attrition over 6 years. CONCLUSIONS: Individuals with delayed circadian rhythm have significantly shorter LTL, but not faster LTL attrition rates.