Multicentre service evaluation of injectable cabotegravir and rilpivirine delivery and outcomes across 12 UK clinics (SHARE LAI-net).

INTRODUCTION: Long-acting injectable cabotegravir + rilpivirine (CAB + RPV LAI) was approved for use in virally suppressed adults in the England and Wales national health service in November 2021. We describe a service evaluation of delivery processes and outcomes in 12 clinics. METHODS: Centres populated a database using information from local policies and clinical records. Services were asked to describe approval processes, clinic pathways, and adherence to national guidelines. Additional data were collected on reasons for regimen choice, treatment discontinuations, and management of viraemia. RESULTS: In total, 518 adults from 12 clinics were approved for CAB + RPV LAI between February 2022 and December 2023. Of the 518 people approved for CAB + RPV LAI, 423 received at least one injection. Median duration on CAB + RPV was 7.5 months (interquartile range 3.7-11.3). In total, 97% of injections were administered within the ±7-day window. Virological failure occurred in 0.7%, and 6% discontinued CAB + RPV. CONCLUSION: In this large UK-based cohort, robust approval processes and clinic protocols facilitated on-time injections and low rates of both discontinuation and virological failure.

Functional Neurologic Disorders, disorders to be managed by neurologists, or are neurologists wandering in a dangerous field with inadequate resources?

In recent years, some neurologists reconsidered their approach to Medically Unexplained Symptoms and proposed Functional Neurologic Disorders (FND) as a new entity, claiming that neurology could offer alternative treatment options to the psychotherapies provided in psychiatry settings. FNDs, for this purpose, should include only the disorders listed as Conversion from the Somatic Symptom and Related Disorders (SSRD) group. The present review analyzes the rationale of this position and challenges the arguments provided for its support. The review also discusses the systematization of these disorders as provided by public health systems. It outlines risks stemming from economic support and public funding uncertainty, given their negligible epidemiological dimensions resulting from the parcellation of SSRD. The review underlines the unresolved issue of Factitious Disorders, which are in the same SSRD category of the international classification but are, nonetheless, overlooked by the theoretical proponents of the FND entity. Comorbidity with other psychiatric disorders is also analyzed. We propose a model that supports the continuum between different SSRD conditions, including Factitious Disorders. The model is based on the emergence of feigned death reflex and deception from frontal lobe dysfunction. Finally, the paper summarizes the wealth of historical psychiatric and psychodynamic approaches and critical reviews. The study also puts in context the categorization and interpretation efforts provided by the most eminent researchers of the past century.

Decline in Hepatitis C Virus (HCV) Incidence in Men Who Have Sex With Men Living With Human Immunodeficiency Virus: Progress to HCV Microelimination in the United Kingdom?

BACKGROUND: Modeling of the London hepatitis C virus (HCV) epidemic in men who have sex with men (MSM) and are living with human immunodeficiency virus (HIV) suggested that early access to direct-acting antiviral (DAA) treatment may reduce incidence. With high rates of linkage to care, microelimination of HCV within MSM living with HIV may be realistic ahead of 2030 World Health Organization targets. We examined trends in HCV incidence in the pre- and post-DAA eras for MSM living with HIV in London and Brighton, United Kingdom. METHODS: A retrospective cohort study was conducted at 5 HIV clinics in London and Brighton between 2013 and 2018. Each site reported all acute HCV episodes during the study period. Treatment timing data were collected. Incidence rates and reinfection proportion were calculated. RESULTS: A total of.378 acute HCV infections were identified, comprising 292 first infections and 86 reinfections. Incidence rates of acute HCV in MSM living with HIV peaked at 14.57/1000 person-years of follow-up (PYFU; 95% confidence interval [CI], 10.95-18.20) in 2015. Rates fell to 4.63/1000 PYFU (95% CI, 2.60 to 6.67) by 2018. Time from diagnosis to starting treatment declined from 29.8 (2013) to 3.7 months (2018). CONCLUSIONS: We observed a 78% reduction in the incidence of first HCV episode and a 68% reduction in overall HCV incidence since the epidemic peak in 2015, which coincides with wider access to DAAs in England. Further interventions to reduce transmission, including earlier access to treatment and for reinfection, are likely needed for microelimination to be achieved in this population.

Prevalence of significant liver disease in human immunodeficiency virus-infected patients exposed to Didanosine: A cross sectional study.

AIM: To identify significant liver disease [including nodular regenerative hyperplasia (NRH)] in asymptomatic Didanosine (DDI) exposed human immunodeficiency virus (HIV) positive patients. METHODS: Patients without known liver disease and with > 6 mo previous DDI use had liver stiffness assessed by transient elastography (TE). Those with alanine transaminase (ALT) above upper limit normal and/or TE > 7.65 kPa underwent ultrasound scan (U/S). Patients with: (1) abnormal U/S; or (2) elevated ALT plus TE > 7.65 kPa; or (3) TE > 9.4 kPa were offered trans-jugular liver biopsy (TJLB) with hepatic venous pressure gradient (HVPG) assessment. RESULTS: Ninety-nine patients were recruited, median age 50 years (range 31-70), 81% male and 70% men who have sex with men. Ninety-five percent with VL < 50 copies on antiretroviral therapy with median CD4 count 639 IU/L. Median DDI exposure was 3.4 years (range 0.5-14.6). Eighty-one had a valid TE readings (interquartile range/score ratio < 0.3): 71 (88%) < 7.65 kPa, 6 (7%) 7.65-9.4 kPa and 4 (6%) > 9.4 kPa. Seventeen (17%) met criteria for TJLB, of whom 12 accepted. All had HVPG < 6 mmHg. Commonest histological findings were steatosis (n = 6), normal architecture (n = 4) and NRH (n = 2), giving a prevalence of previously undiagnosed NRH of 2% (95%CI: 0.55%, 7.0%). CONCLUSION: A screening strategy based on TE, liver enzymes and U/S scan found a low prevalence of previously undiagnosed NRH in DDI exposed, asymptomatic HIV positive patients. Patients were more likely to have steatosis highlighting the increased risk of multifactorial liver disease in this population.

Binding action and emotion in first-episode schizophrenia.

BACKGROUND/AIMS: Several components of social cognition are compromised in schizophrenia (SCZ) from the early stage of the illness. In this study we first investigated whether mirror neuron-driven embodied simulation (mnES) is altered in first-episode SCZ. Second, we tested whether emotional cues impact on the mnES in SCZ patients. METHODS: Twenty-two SCZ patients and 22 healthy controls (HCs) observed goal-related actions in either a neutral or emotional context during functional magnetic resonance imaging scanning. RESULTS: Observation of neutral action elicited a lower activity in the frontoparietal network in SCZ patients, as compared to HCs. Particularly, activation in the left inferior parietal lobule in response to the same condition negatively correlated with patients' self-experience disturbances. Moreover, observation of an action performed by an angry agent produced poorer neural activity in the right anterior insula in SCZ patients as compared to HCs. This difference was mostly due to the negative ß-values shown by SCZ patients, which positively correlated with their empathy scores. No differences were found contingent upon the observation of an action performed by a happy agent. CONCLUSION: Our results show that emotional cues allow SCZ patients to partially recover mnES. However, their understanding of the emotional components of the actions of others will likely remain deficient.

Altered brain long-range functional interactions underlying the link between aberrant self-experience and self-other relationship in first-episode schizophrenia.

Self-experience anomalies are elementary features of schizophrenic pathology. Such deficits can have a profound impact on self-other relationship, but how they are related through aberrant brain function remains poorly understood. In this functional magnetic resonance imaging (fMRI) study, we provide new evidence for a cortical link between aberrant self-experience and social cognition in first-episode schizophrenia (FES). As identified in previous studies, ventral premotor cortex (vPMC) and posterior insula (pIC) are candidate brain regions underlying disturbances in both self-experience and self-other relationship due to their processing of predominantly externally guided (vPMC; goal-oriented behavior) and internally guided (pIC; interoception) stimuli. Results from functional interaction analysis in a sample of 24 FES patients and 22 healthy controls show aberrant functional interactions (background/intrinsic connectivity) of right vPMC and bilateral pIC with posterior cingulate cortex (PCC), a midline region that has been shown central in mediating self-experience. More specifically, our results show increased functional coupling between vPMC and PCC, which positively correlated with basic symptoms (subjective self-experience disturbances). pIC showed reduced functional coupling with PCC and postcentral gyrus and increased functional interactions with anterior insula. Taken together, our results suggest an imbalance in the processing between internally and externally guided information and its abnormal integration with self-referential processing as mediated by PCC. Due to our correlation findings, we suggest this imbalance to be closely related to basic symptoms in FES and thus anomalous self-experience. The findings further disentangle the cortical basis of how self-experience anomalies may pervade the social domain.

Binding action and emotion in social understanding.

In social life actions are tightly linked with emotions. The integration of affective- and action-related information has to be considered as a fundamental component of appropriate social understanding. The present functional magnetic resonance imaging study aimed at investigating whether an emotion (Happiness, Anger or Neutral) dynamically expressed by an observed agent modulates brain activity underlying the perception of his grasping action. As control stimuli, participants observed the same agent either only expressing an emotion or only performing a grasping action. Our results showed that the observation of an action embedded in an emotional context (agent's facial expression), compared with the observation of the same action embedded in a neutral context, elicits higher neural response at the level of motor frontal cortices, temporal and occipital cortices, bilaterally. Particularly, the dynamic facial expression of anger modulates the re-enactment of a motor representation of the observed action. This is supported by the evidence that observing actions embedded in the context of anger, but not happiness, compared with a neutral context, elicits stronger activity in the bilateral pre-central gyrus and inferior frontal gyrus, besides the pre-supplementary motor area, a region playing a central role in motor control. Angry faces not only seem to modulate the simulation of actions, but may also trigger motor reaction. These findings suggest that emotions exert a modulatory role on action observation in different cortical areas involved in action processing.

Out of touch with reality? Social perception in first-episode schizophrenia.

Social dysfunction has been recognized as an elementary feature of schizophrenia, but it remains a crucial issue whether social deficits in schizophrenia concern the inter-subjective domain or primarily have their roots in disturbances of self-experience. Social perception comprises vicarious processes grounding an experiential inter-relationship with others as well as self-regulation processes allowing to maintain a coherent sense of self. The present study investigated whether the functional neural basis underlying these processes is altered in first-episode schizophrenia (FES). Twenty-four FES patients and 22 healthy control participants underwent functional magnetic resonance imaging during a social perception task requiring them to watch videos depicting other individuals' inanimate and animate/social tactile stimulations, and a tactile localizer condition. Activation in ventral premotor cortex for observed bodily tactile stimulations was reduced in the FES group and negatively correlated with self-experience disturbances. Moreover, FES patients showed aberrant differential activation in posterior insula for first-person tactile experiences and observed affective tactile stimulations. These findings suggest that social perception in FES at a pre-reflective level is characterized by disturbances of self-experience, including impaired multisensory representations and self-other distinction. However, the results also show that social perception in FES involves more complex alterations of neural activation at multiple processing levels.

Impaired sustained attention in euthymic bipolar disorder patients and non-affected relatives: an fMRI study.

OBJECTIVE: Behavioral deficits in sustained attention have been reported during both acute and euthymic phases of type I bipolar disorder (BD-I) and also in non-affected relatives of bipolar disorder (BD) patients. In particular, selective failure in target recognition was proposed as a potential trait marker for BD, but there are few studies exploring the neural correlates. The aim of the present study was to analyze the behavioral and functional magnetic resonance imaging (fMRI) response of euthymic BD-I patients and non-affected relatives during a sustained attention task. METHODS: Twenty-four euthymic BD-I patients, 22 non-affected first-degree relatives of BD-I subjects, and 24 matched controls underwent a continuous performance test (CPT) with two levels of difficulty during event-related fMRI scanning. RESULTS: Both patients and relatives showed a lower accuracy in target detection when compared to controls. The fMRI data analysis revealed between-group differences in several brain regions involved in sustained attention. During error in target recognition, both patients and relatives showed a larger activation in the bilateral insula and the posterior part of the middle cingulate cortex. By contrast, during correct target response, only patients failed to activate the right insula, whereas relatives showed an increased activation of the left insula and bilateral inferior parietal lobule - limited to the higher attention load - and an augmented deactivation of the posterior cingulate/retrosplenial cortex. CONCLUSIONS: A selective impairment in target recognition during a CPT was behaviorally and functionally detectable in both euthymic BD-I patients and non-affected first-degree relatives, suggesting that specific sustained attention deficits may be a potential trait marker for BD-I.

Bodily self and schizophrenia: the loss of implicit self-body knowledge.

Schizophrenia spectrum has been associated with a disruption of the basic sense of self, which pertains, among others, the representation of one's own body. We investigated the impact of either implicit or explicit access to the representation of one's own body-effectors on bodily self-awareness, in first-episode schizophrenia (FES) patients and healthy controls (HCs). We contrasted their performance in an implicit self-recognition task (visual matching) and in an explicit self/other discrimination task. Both tasks employed participant's own and others' body-effectors. Concerning the implicit task, HCs were more accurate with their own than with others' body-effectors, whereas patients did not show such self-advantage. Regarding the explicit task, both groups did not exhibit a self-advantage, and patients showed a higher percentage of self-misattribution errors. Neither self/other nor implicit/explicit effects were found in both groups when processing inanimate-objects. We propose that FES patients suffer of a disturbed implicit sense of bodily self.

Action verb understanding in first-episode schizophrenia: is there evidence for a simulation deficit?

Schizophrenia is often associated with deficits in the domain of language, which are thought to be closely related to deficits in the structure of semantic knowledge. The main aim of the present study was to behaviorally investigate whether semantic impairments in schizophrenia are present also at the very basic level of action verb processing, in particular at the level of motor simulation. We used a go-no go paradigm both for a semantic decision task (with either an early, EGD, or a delayed go-signal delivery, DGD) and for a lexical decision task (control task). Only the first task requires motor simulation to be solved. We found that first-episode schizophrenia (FES) patients, like healthy control (HC) participants, use motor simulation as a basic strategy to semantically judge action verbs. In the EGD condition, both motor simulation and action verb understanding seem to be preserved in FES. However, differently from HC participants, FES patients kept on using the simulation strategy also with the DGD condition, whereas, simultaneously, task performance during this condition appeared to be less efficient and sensitive. Voxel-based morphometry analysis suggested that this altered performance in FES patients could be related to structural brain abnormalities in the right dorsolateral prefrontal cortex. We propose that a prolonged motor simulation in FES may serve as a compensatory strategy for impairments in the selection of action representation and/or for memory deficits disclosed by the DGD condition during the semantic decision task investigated in the present study.

Differential involvement of somatosensory and interoceptive cortices during the observation of affective touch.

Previous studies suggested that the observation of other individuals' somatosensory experiences also activates brain circuits processing one's own somatosensory experiences. However, it is unclear whether cortical regions involved with the elementary stages of touch processing are also involved in the automatic coding of the affective consequences of observed touch and to which extent they show overlapping activation for somatosensory experiences of self and others. In order to investigate these issues, in the present fMRI study, healthy participants either experienced touch or watched videos depicting other individuals' inanimate and animate/social touch experiences. Essentially, a distinction can be made between exteroceptive and interoceptive components of touch processing, involved with physical stimulus characteristics and internal feeling states, respectively. Consistent with this distinction, a specific negative modulation was found in the posterior insula by the mere visual perception of other individuals' social or affective cutaneous experiences, compared to neutral inanimate touch. On the other hand, activation in secondary somatosensory and posterior superior temporal regions, strongest for the most intense stimuli, seemed more dependent on the observed physical stimulus characteristics. In contrast to the detected vicarious activation in somatosensory regions, opposite activation patterns for the experience (positive modulation) and observation (negative modulation) of touch suggest that the posterior insula does not reflect a shared representation of self and others' experiences. Embedded in a distributed network of brain regions underpinning a sense of the bodily self, the posterior insula rather appears to differentiate between self and other conditions when affective experiences are implicated.

Altered brain response without behavioral attention deficits in healthy siblings of schizophrenic patients: an event-related fMRI study.

Attention deficits are common in schizophrenics and sometimes reported in their healthy relatives. The aim of this study was to analyse the behavioural performance and the brain activation of healthy siblings of schizophrenic patients during a sustained-attention task. Eleven healthy siblings of schizophrenic patients and eleven matched controls performed a Continuous Performance Test (CPT), during 1.5 T fMRI. The stimuli were presented at three difficulty-levels, using different degrees of degradation (0, 25 and 40%). There were no significant differences in CPT performance (mean reaction time and percentage of errors) between the two groups. Performance worsened with increasing degradation in both groups. Differences were found when comparing the BOLD signal change in the medial frontal gyrus/dorsal anterior cingulate, right precentral gyrus, bilateral posterior cingulate and bilateral insula. The most evident between group differences were observed in the left insula/inferior frontal gyrus: siblings showed a larger activation during wrong responses and a reduced activation during correct responses in the degraded runs. In conclusion, healthy siblings of schizophrenic patients showed differences in brain function in several brain regions previously reported in schizophrenic subjects, in the absence of behavioral attention deficits. The differences were greater in the two more difficult levels of attention demand and might be expressions of altered and/or compensatory mechanisms in subjects at increased risk for schizophrenia.

Alexithymia and its relationships with dissociative experiences and Internet addiction in a nonclinical sample.

The aim of the present study was to evaluate alexithymia, dissociative experiences, and Internet addiction (IA) in a nonclinical sample of 312 undergraduate students, identifying predictive factors associated with the possible risk of developing IA. We found that alexithymics had more consistent dissociative experiences, lower self-esteem, and higher obsessive-compulsive symptoms than nonalexithymics. In addition, alexithymics reported a higher potential risk for IA when compared to nonalexithymics. Difficulty in identifying feelings, higher dissociative experiences, lower self-esteem, and higher impulse dysregulation were associated with higher IA. Thus, a combination of alexithymia, dissociative experiences, low self-esteem, and impulse dysregulation may be a risk factor for IA, at least in a nonclinical sample.

Alexithymia and its relationships with C-reactive protein and serum lipid levels among drug naïve adult outpatients with major depression.

Several studies have investigated the relationship between C-reactive protein (CRP) and serum lipid levels in Major Depression (MD), but no study has, to date, evaluated the impact of alexithymia on these parameters. Therefore, the aim of the present cross-sectional study was to evaluate the relationship between alexithymia, suicide risk, C-reactive protein (CRP) and serum lipid levels in adult outpatients suffering from moderate to severe MD. CRP and serum lipid levels data were analyzed in 145 drug-naïve adult outpatients (69 men, 76 women) with a DSM-IV diagnosis of MD. Alexithymia was measured with the 20-item Toronto Alexithymia Scale (TAS-20), depression severity was evaluated with the 17-item Hamilton Depression Rating Scale (HAM-D) and suicide risk was determined using the Scale of Suicide Ideation (SSI). Alexithymics showed altered serum lipid levels and higher CRP than non-alexithymics. In the linear regression models, lower total cholesterol levels and "Difficulty in Identifying Feelings" dimension of TAS-20 were significantly associated with depression severity, whereas lower high-density lipoprotein levels and "Difficulty in Identifying and Describing Feelings" dimensions of TAS-20 were associated with higher suicide risk. Authors discuss study limitations and future research needs.

Epilepsy and suicide: pathogenesis, risk factors, and prevention.

Depression and suicide tendencies are common in chronic diseases, especially in epilepsy and diabetes. Suicide is one of the most important causes of death, and is usually underestimated. We have analyzed several studies that compare mortality as a result of suicide in epileptic patients and in the general population. All the studies show that epileptic patients have a stronger tendency toward suicide than healthy controls. Moreover it seems that some kinds of epilepsy have a higher risk for suicide (temporal-lobe epilepsy). Among the risk factors are surgery therapy (suicide tendency five times higher than patients in pharmacological therapy), absence of seizures for a long time, especially after being very frequent, and psychiatric comorbidity (major depression, anxiety-depression disorders, personality disorders, substance abuse, psychoses). The aim of the review was to analyze the relationship between suicide and epilepsy, to identify the major risk factors, and to analyze effective treatment options.

Insight and perceived expressed emotion among adult outpatients with obsessive-compulsive disorder.

OBJECTIVE: To elucidate the relationships between insight and perceived expressed emotion (EE) in a sample of adult outpatients with obsessive-compulsive disorder (OCD). METHODS: The study involved 75 subjects with OCD. Subjects were assessed with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), with the score on item 11 used as a measure of insight level. Perceived EE was evaluated using the Family Emotional Involvement and Criticism Scale (FEICS). The Montgomery Asberg Depression Rating Scale (MADRS) was used to evaluate depressive symptoms. RESULTS: Poor or absent insight was found to be associated with higher perceived EE and significantly higher OCD severity, as well higher familial perceived criticism and more compulsions and depressive symptoms.

The role of duloxetine in the treatment of anxiety disorders.

Anxiety disorders (ADs) are the most common type of psychiatric disorders, with a mean incidence of 18.1% and a lifetime prevalence of 28.8%. Pharmacologic options studied for treating ADs may include benzodiazepines, tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRIs), noradrenergic and specific serotonergic drug (NaSSA) and dual-reuptake inhibitors of serotonin and norepinephrine (SNRIs). In this context, the development of SNRIs (venlafaxine and duloxetine) has been particularly useful. As a dual-acting intervention that targets two neurotransmitter systems, these medications would appePar promising for the treatment of ADs. The purpose of this review was to elucidate current facts and views about the role of duloxetine in the treatment of ADs. In February 2007, duloxetine was approved by FDA for the treatment of generalized anxiety disorder (GAD). The results of trials evaluating the use duloxetine in the treatment of GAD are supportive on its efficacy even if further studies on long-term use are needed. Apart from some interesting case reports, no large studies are, to date, present in literature about duloxetine and other ADs such as panic disorder, social anxiety disorder, obsessive-compulsive disorder and post-traumatic stress disorder. Therefore, the clinical efficacy and the relative good tolerability of duloxetine may be further investigated to widen the therapeutic spectrum of ADs.

Alexithymia and its relationships with body checking and body image in a non-clinical female sample.

The aim of the present study was to evaluate in a non-clinical sample of undergraduate women, the relationships between alexithymia, body checking and body image, identifying predictive factors associated with the possible risk of developing an Eating Disorder (ED). The Toronto Alexithymia Scale (TAS-20), Body Checking Questionnaire (BCQ), Eating Attitudes Test (EAT-26), Body Shape Questionnaire (BSQ), Interaction Anxiousness Scale (IAS), Rosenberg Self-Esteem Scale (RSES) and the Beck Depression Inventory (BDI) were completed by 254 undergraduate females. We found that alexithymics had more consistent body checking behaviors and higher body dissatisfaction than nonalexithymics. In addition, alexithymics also reported a higher potential risk for ED (higher scores on EAT-26) when compared to nonalexithymics. Difficulty in identifying and describing feelings subscales of TAS-20, Overall appearance and Specific Body Parts subscales of BCQ as well as lower self-esteem was associated with higher ED risk in a linear regression analysis. Thus, a combination of alexithymia, low self-esteem, body checking behaviors and body dissatisfaction may be a risk factor for symptoms of ED at least in a non-clinical sample of university women.