Treatment-refractory Symptoms Research Articles

Longitudinal evaluation of the early auditory gamma-band response and its modulation by attention in first-episode psychosis.

Executive control over low-level information processing is impaired proximal to psychosis onset with evidence of recovery over the first year of illness. However, previous studies demonstrating diminished perceptual modulation via attention are complicated by simultaneously impaired perceptual responses. The present study examined the early auditory gamma-band response (EAGBR), a marker of early cortical processing that appears preserved in first-episode psychosis (FEP), and its modulation by attention in a longitudinal FEP sample. Magnetoencephalography was recorded from 25 FEP and 32 healthy controls (HC) during active and passive listening conditions in an auditory oddball task at baseline and follow-up (4-12 months) sessions. EAGBR inter-trial phase coherence (ITPC) and evoked power were measured from responses to standard tones. Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). There was no group difference in EAGBR power or ITPC. While EAGBR ITPC increased with attention in HC, this modulation was impaired among FEP. Diminished EAGBR modulation in FEP persisted at longitudinal follow-up. However, among FEP, recovery of EAGBR modulation was associated with reduced PANSS negative scores. FEP exhibit impaired executive control over the flow of information at the earliest stages of sensory processing within auditory cortex. In contrast to previous work, this deficit was observed despite an intact measure of sensory processing, mitigating potential confounds. Recovery of sensory gain modulation over time was associated with reductions in negative symptoms, highlighting a source of potential resiliency against some of the most debilitating and treatment refractory symptoms in early psychosis.

Comparing clinical success and procedural difficulty between treatment-naïve and treatment-refractory patients with esophageal motility disorders during peroral endoscopic myotomy.

Peroral endoscopic myotomy (POEM) can successfully treat patients with achalasia. Prior therapy with Botox (Allergan, Madison, NJ, USA) injections, pneumatic dilation (PD), and/or laparoscopic Heller myotomy (LHM) is believed to increase the difficulty of POEM procedures. We aimed to determine if prior treatment methods were associated with longer procedure times or lower clinical success. In this single-center retrospective study, consecutive patients who underwent POEM for achalasia between February 2017 and September 2021 were studied. Collected data were patient demographics, prior treatment, pre- and postprocedure Eckardt score (ES), distensibility indices (DIs), and procedure times. Primary outcomes were clinical success and procedure difficulty. Of 95 patients (mean age, 55.6 years; 45% women), 25 patients underwent POEM for type I achalasia, 31 for type II achalasia, and 33 for spastic esophageal pathologies. Thirty-three patients (34.7%) were treated for achalasia before POEM with onabotulinumtoxinA injections (n= 18), PD (n= 17), and LHM (n= 3). There were no significant differences in post-treatment ESs or technical success between the 2 groups (P= .98 and P= .66, respectively). Multivariate analysis showed that prior treatment was associated with decreased case time and easier tunneling during POEM. Prior treatment did not impact the clinical success rate of POEM and led to decreased case times and easier tunneling difficulty, likely because of persistent lower esophageal sphincter changes and differences in diagnostic indications. POEM should be considered for patients with treatment-refractory symptoms as a safe and feasible option. Further large-scale studies are needed to validate our findings.

Longitudinal Investigation of Auditory Dynamic Range Deficits in Early Psychosis and its Relationship to Negative Symptoms.

Despite accounting for significant disease morbidity in schizophrenia, the neuropathological basis of negative symptoms remains poorly understood and options for treatment limited. Our recent study identified robust associations between diminished auditory cortex (AC) dynamic range and social functioning impairments and negative symptoms in first episode psychosis (FESz). The current investigation examined the progression of these relationships 4-8 months from baseline testing. Twenty-six FESz and 38 healthy controls (HC) were tested at baseline and follow-up. Magnetoencephalography (MEG) was recorded during binaural presentation of tones (75, 80, and 85 dB). Assessments included the MATRICS cognitive consensus battery (MCCB) and Global Functioning: Role and Social scales (GFR/GFS) and the Positive and Negative Syndrome Scale. Overall, FESz exhibited a blunted response to increasing tone intensity relative to HC. While this deficit did not change over time at the group level, recovery of right hemisphere AC dynamic range (85-75 dB response) among FESz individuals was associated with reductions in negative symptoms (ρ = -0.50). Diminished dynamic range was also associated with impaired GFS (ρ = 0.65), GFR (ρ = 0.51), and MCCB (ρ = 0.49) at baseline and increased negative symptoms at baseline (ρ = -0.53) and follow-up (ρ = -0.51). Despite persistent dynamic range impairment in FESz as a group, individual recovery of this AC response property was associated with significant reduction in negative symptoms. Identification of a functional neural deficit that tracts progression of negative symptoms during a critical period for disease modification is essential to the management of these devastating and historically treatment refractory symptoms.

“Life, Interrupted”: A Patient Experience Encompassing the Journey From Hospital to the Community, With Support From the Mental Health Intensive Support Team (MhIST)

AimsWe present outcomes of a newly developed Community Rehabilitation team (MhIST) using the context of Jen's personal story. Jen is a 31-year-old student and freelance journalist. This story encompasses her journey from inpatient rehabilitation services to the community, completed with support from MhIST.Methods“For nearly four years, I was sectioned under the Mental Health Act as an inpatient in hospital. As I had been denied my fundamental liberties for so long, the prospect of leaving hospital for good and enjoying total freedom was both exhilarating and terrifying. How would I fare in the community, living on my own? Would I be lonely? Would I relapse? Would I survive?”Upon leaving hospital, I immediately received intensive support from MhIST. They were the bridge between the gulf that was hospital and the community. Since leaving hospital, I have been relishing my freedom. I enjoy meeting up with my friends after so long apart. I have volunteered at The Storyhouse, a local arts venue. The Spider Project – a non-clinical community mental health service in Chester - has also provided me with fulfilling activities from yoga to creative writing. The MHIST team have not only kept me well but, most importantly, helped me thrive. Leaving hospital has been an adventure. It has been a joy to regain my independence and freedom. To live rather than to exist. Life is amazing. Long may it continue.”ResultsMhIST provides an intensive rehabilitation and recovery service, delivering bespoke packages of care to individuals. This is achieved using key working and a shared team approach, outcome focused goal-based interventions, weekly reflective/formulation meetings, and a focus on social rehabilitation. Patients referred to MhIST will have a high level of complexity plus severe, treatment refractory symptoms, with impaired social, interpersonal and occupational function and high support needs. They may have co-occurring mental health conditions including substance misuse or neurodevelopmental disorders.MhIST is a new service and has been active for around 6 months. The first 10 patients referred have been from acute wards (3), community mental health teams (1), and inpatient rehabilitation wards (6). 60% of patients are currently housed in independent accommodation.ConclusionJen's story narrates the experience she encountered during transition from inpatient rehabilitation services to the community. This was completed with support from MhIST, a new community rehabilitation service which provides an intensive rehabilitation and recovery service.

Low-dose intrathecal rituximab is a safe and potentially effective treatment for pediatric neuroimmunologic disorders

Historically, treatment options for refractory neuroimmunologic disorders have been limited. Use of intrathecal rituximab has been described in a few case reports but experience in pediatric patients is limited. Here, we report our experience with intrathecal rituximab in 5 pediatric patients with refractory neuroimmunologic conditions. Patients were identified based on treatment-refractory symptoms despite first and second-line therapies and treated according to a standardized protocol. Although individual outcomes varied, intrathecal rituximab showed a favorable safety profile and was well-tolerated. Three out of five patients showed evidence of a positive clinical response assessed by modified Rankin score or Mitchell-Pike Opsoclonus-Myoclonus score. Findings from this retrospective observational study suggest that intrathecal rituximab is a safe and potentially effective therapy in carefully selected patients with refractory neuroimmunologic disorders despite appropriate first and second-line therapies.

Interacting Roles of COMT and GAD1 Genes in Patients with Treatment-Resistant Schizophrenia: a Genetic Association Study of Schizophrenia Patients and Healthy Controls.

The projection from dopaminergic neurons to gamma-aminobutyric acid (GABA) interneurons in the prefrontal cortex is involved in the etiology of schizophrenia. The impact of interacting effects between dopamine signals and the expression of GABA on the clinical phenotypes of schizophrenia has not been studied. Since these interactions could be closely involved in prefrontal cortex functions, patients with specific alleles of these relevant molecules (which lead to lower or vulnerable genetic functions) may develop treatment-refractory symptoms. We conducted a genetic association study focusing on COMT and GAD1 genes for a treatment-resistant schizophrenia (TRS) group (n=171), a non-TRS group (n=592), and healthy controls (HC: n=447), and we examined allelic combinations specific to TRS. The results revealed that the percentage of subjects with Met allele of rs4680 on the COMT gene and C/C homozygote of rs3470934 on the GAD1 gene was significantly higher in the TRS group than the other two groups. There was no significant difference between the non-TRS group and HC groups. Considering the direction of functions of these single-nucleotide polymorphisms revealed by previous studies, we speculate that subjects with the Met/CC allelic combination could have a higher dopamine level and a lower expression of GABA in the prefrontal cortex. Our results suggest that an interaction between the dopaminergic signal and GABA signal intensities could differ between TRS patients and patients with other types of schizophrenia and healthy subjects.

Sedation in palliative care - step by step

Sedation in palliative care, also called "palliative sedation", is an important treatment option for patients who experience unbearable suffering from treatment-refractory symptoms at the end of life. The aim is to reduce this suffering as far as possible by reduction of the patient's consciousness. Good communication between all people involved is crucial for these clinically and ethically challenging situations. This article presents definitions of key terms and of different types of sedation. It then describes the process of sedation step by step: 0. Pre-emptive discussion of the option of sedation (in the context of advance care planning); 1. indication and decision making; 2. information and informed consent; 3. documentation when starting sedation; 4. start of sedation; 5. monitoring and adaption of sedation; 6. medical and nursing care and documentation during sedation; 7. care and processes after the death of the patient (if applicable).

Clozapine-induced parotitis: A case study

IntroductionClozapine is the drug of choice for patients with an unsatisfactory response to classic antipsychotic treatment. Little is known about the involvement of clozapine in the development of parotid disease.ObjectivesIdentify the clinical characteristics of Clozapine-induced parotitis through a case and literature review.MethodsWe report the case of a patient with a refractory schizoaffective disorder, bipolar type and who developed recurrent parotitis while taking clozapine. We conducted a literature review based on a PubMed search of articles published on this subject with the following keywords: ‘parotitis clozapine’.ResultsMiss W., 34 years old, suffers from a severe schizoaffective disorder that has been diagnosed for several years. She has received various psychotropic medications. She suffered from frequent relapses that required recurrent hospital admissions. One year ago, a diagnosis of treatment-resistant schizoaffective disorder was made. The decision to introduce clozapine, associated with mood stabilizer treatment, was made on the basis of her treatment refractory symptoms. She experienced considerable sialorrhea after beginning clozapine treatment. Miss W. developed bilateral recurrent swelling over both temporal-mandibular areas after 6 months of treatment. It often appears after eating and lasts from 4 to 6 hours. There was no change in white blood cell count and she was afebrile. An otolaryngologist was consulted and a diagnosis of clozapine-induced parotitis was suggested. A spasmolytic and an anticholinergic treatment were prescribed and clozapine was continued.ConclusionsThis iatrogenic effect of clozapine must be recognized by clinicians in order to be better prevented.

On Neuropsychiatric Manifestations of Basal Ganglia Injury: A Report of Three Cases and Literature Review

The basal ganglia have been considered to primarily play a role in motor processing. A growing body of theoretical and clinical evidence shows that in addition to the motor functions the basal ganglia play a key role in perceptual and visual disturbances. This role may be evident in patients with basal ganglia pathology and subsequent manifestation of symptoms that include cognitive, perceptual, and affective disturbances. We present three cases with basal ganglia pathology that demonstrate affective and psychotic symptoms. Two of the cases presented with late onset psychotic disturbances suggesting likely neurological etiologies. The third case presented with treatment refractory psychosis and symptoms that are rare for a diagnosis of schizophrenia. The role of incidental bilateral basal ganglia calcifications in all the cases is discussed. A review of current literature highlighting various neuropsychiatric manifestations of basal ganglia pathologies in various patients with psychiatric symptoms is presented.

The Role of Caregiver Psychopathology in the Treatment of Childhood Trauma with Trauma-Focused Cognitive Behavioral Therapy: A Systematic Review.

Trauma-focused cognitive behavioral therapy (TF-CBT) is regarded as one of the most effective treatments for children who have experienced trauma and is rapidly being disseminated. To best ensure efficacy, even among treatment refractory symptoms, a better understanding of the factors that lead TF-CBT to be more or less effective for some children is warranted. One major factor that has not been systematically considered is the role of caregiver psychopathology. Therefore, this systematic review of 18 empirical studies examined how TF-CBT has incorporated caregiver psychopathology into the treatment of childhood trauma and how it is related to treatment outcomes. The results of this review provide preliminary support for TF-CBT decreasing caregiver psychopathology, in terms of symptoms of depression, PTSD, and emotional distress related to the child's experience of trauma, as well as partial support for caregiver depression, rather than caregiver PTSD or distress, influencing child treatment outcomes. It also illuminates the strong need for future TF-CBT studies to routinely measure caregiver psychopathology. Several recommendations are provided to ensure that the emerging research base can inform clinical practice guidelines on how to incorporate caregivers who exhibit psychopathology and potentially develop modifications to the existing treatment to address trauma and symptoms in both members of the caregiver-child dyad, when needed.

An Open-Labeled Study on Fecal Microbiota Transfer in Irritable Bowel Syndrome Patients Reveals Improvement in Abdominal Pain Associated with the Relative Abundance of Akkermansia Muciniphila

Background/Aims: The gut microbiota is altered in irritable bowel syndrome (IBS), and microbiota manipulations by diet or antibiotics can reduce its symptoms. As fecal microbiota transfer (FMT) in IBS is still controversial, we investigated the clinical and side effects of FMT in a cohort of IBS patients with recurrent, treatment refractory symptoms, and studied gut microbiota signatures. Methods: Using an observational, prospective study design, we applied FMTs from one unrelated, healthy donor to 13 IBS patients. Fecal samples of patients and the donor were analyzed by 16S ribosomal RNA amplicon sequencing. Results: On a symptom level, primarily abdominal pain symptoms were reduced after FMT, and no adverse effects were observed. Studying the microbiome, we found an increase in alpha diversity and changes in the composition of the gut microbiota after FMT. Beta diversity changes after FMT were prominent in a subset of 7 patients with microbiota profiles coming very close to the donor. These patients also showed most pronounced visceral pain reduction. The relative abundance of Akkermansia muciniphila was inversely correlated with pain reduction in our cohort. Conclusion: Although exploratory in nature and with a pilot character, this study highlights the potential role of microbiota manipulations in IBS and describes a novel association of intestinal Akkermansia and pain modulation.

Clinical Trials and Therapeutic Rationale for Drug Repurposing in Schizophrenia.

There is a paucity of efficacious novel drugs to address high rates of treatment resistance and refractory symptoms in schizophrenia. The identification of novel therapeutic indications for approved drugs-drug repurposing-has the potential to expedite clinical trials and reduce the costly risk of failure which currently limits central nervous system drug discovery efforts. In the present Review we discuss the historical role of drug repurposing in schizophrenia drug discovery and review the main classes of repurposing candidates currently in clinical trials for schizophrenia in terms of their therapeutic rationale, mechanisms of action, and preliminary results from clinical trials. Subsequently we outline the challenges and limitations which face the clinical repurposing pipeline and how novel technologies might serve to address these.

Improvement in Gastrointestinal Symptoms After Cognitive Behavior Therapy for Refractory Irritable Bowel Syndrome

There is an urgent need for safe treatments for irritable bowel syndrome (IBS) that relieve treatment-refractory symptoms and their societal and economic burden. Cognitive behavior therapy (CBT) is an effective treatment that has not been broadly adopted into routine clinical practice. We performed a randomized controlled trial to assess clinical responses to home-based CBT compared with clinic-based CBT and patient education. We performed a prospective study of 436 patients with IBS, based on Rome III criteria, at 2 tertiary centers from August 23, 2010, through October 21, 2016. Subjects (41.4 ± 14.8 years old; 80% women) were randomly assigned to groups that received the following: standard-CBT (S-CBT, n= 146, comprising 10 weekly, 60-minute sessions that emphasized the provision of information about brain-gut interactions; self-monitoring of symptoms, their triggers, and consequences; muscle relaxation; worry control; flexible problem solving; and relapse prevention training), or 4 sessions of primarily home-based CBT requiring minimal therapist contact (MC-CBT, n= 145), in which patients received home-study materials covering the same procedures as S-CBT), or 4 sessions of IBS education (EDU, n= 145) that provided support and information about IBS and the role of lifestyle factors such as stress, diet, and exercise. The primary outcome was global improvement of IBS symptoms, based on the IBS-version of the Clinical Global Impressions-Improvement Scale. Ratings were performed by patients and board-certified gastroenterologists blinded to treatment allocation. Efficacy data were collected 2 weeks, 3 months, and 6 months after treatment completion. A higher proportion of patients receiving MC-CBT reported moderate to substantial improvement in gastrointestinal symptoms 2 weeks after treatment (61.0% based on ratings by patients and 55.7% based on ratings by gastroenterologists) than those receiving EDU (43.5% based on ratings patients and 40.4% based on ratings by gastroenterologists) (P < .05). Gastrointestinal symptom improvement, rated by gastroenterologists, 6 months after the end of treatment also differed significantly between the MC-CBT (58.4%) and EDU groups (44.8%) (P= .05). Formal equivalence testing applied across multiple contrasts indicated that MC-CBT is at least as effective as S-CBT in improving IBS symptoms. Patients tended to be more satisfied with CBT vs EDU (P < .05) based on immediate posttreatment responses to the Client Satisfaction Questionnaire. Symptom improvement was not significantly related to concomitant use of medications. In a randomized controlled trial, we found that a primarily home-based version of CBT produced significant and sustained gastrointestinal symptom improvement for patients with IBS compared with education. Clinicaltrials.gov no.: NCT00738920.

Treatment Refractory Ocular Symptoms in Myasthenia Gravis: Clinical and Therapeutic Profile (P6.445)

Treatment Refractory Ocular Symptoms in Myasthenia Gravis: Clinical and Therapeutic Profile (P6.445)

The Clozapine Clinic: A Model of Integrated Care

Introduction: A significant proportion of individuals with psychotic illness are either refractory to, or intolerant of, standard antipsychotic pharmacotherapy. There is currently only one medication available with proven effectiveness in this population. Clozapine while providing a superior response rate requires significant physical health care monitoring both before and during treatment. The medication requires weekly hematologic monitoring and intensive metabolic screening. Methods: A site was selected for establishment of a new Clozapine Clinic to provide services for individuals with treatment refractory psychotic symptoms or individuals with medication side effects deemed to be related to standard antipsychotic medications. Individuals were selected without predetermined exclusion criteria such as age or physical comorbidity. Patients were accepted into the Clozapine Clinic with a combination of physical health and mental health assessments. The Clozapine Clinic was fortunately located in close proximity to a County Primary Care Clinic and County Tertiary Care Hospital, both of which were helpful in obtaining baseline physical health assessments and diagnostic tests and concurrent hematologic and metabolic laboratory monitoring Results: A new Clozapine Medication Support service line was established using a collaborative care model with existing County facilities. At total of 10 new and established individuals were enrolled into the Clozapine Clinic, with weekly, biweekly and monthly psychiatric and physical health monitoring. The Clozapine Clinic continues to receive referrals for individuals in need of complex care with this unique psychopharmacologic agent. Conclusions: Clozapine pharmacotherapy for treatment resistant psychotic symptoms provides a model for integrated care in this population. Using a collaborative relationship and employing integrated care principles as the model, the complex care of new and established Clozapine patients was provided at an existing County Mental Health Clinic. Weekly hematologic and metabolic monitoring was achieved by partnering with the affiliated hospital laboratory in order to provide rapid, same day results. A dedicated Clozapine Clinic Nurse was employed to provide the coordination of physical health assessments, psychiatric evaluations and laboratory monitoring. In less than a year, the Clozapine Clinic services at this clinical site were expanded to approximately 10 individuals, with additional individuals awaiting entry. Clozapine pharmacotherapy for treatment refractory psychiatric illness is vastly underutilized in large part due to the complexity in coordination of physical health and mental health needs. This underutilization leads to high levels of morbidity and mortality in the psychiatric population. Implications for Integrated Care Practice: Since a significant percentage of patients with chronic psychotic illness are either intolerant or refractory to standard antipsychotic medications, Clozapine remains the only effective agent available. However, with its significant need for monitoring of physical health side effects, integrated care models of treatment provide the most cost effective, efficient and comprehensive model for addressing the whole person health care needs of this special population. Integrated Care models represent the solution to the underutilization of Clozapine pharmacotherapy in treatment resistant populations.

A Survey of Hospice and Palliative Care Clinicians' Experiences and Attitudes Regarding the Use of Palliative Sedation.

A variety of terms and attitudes surround palliative sedation (PS) with little research devoted to hospice and palliative care (HPC) clinicians' perceptions and experiences with PS. These factors may contribute to the wide variability in the reported prevalence of PS. This study was designed to better identify hospice and palliative care (HPC) clinician attitudes toward, and clinical experiences with palliative sedation (PS). A 32-question survey was distributed to members of the American Academy of Hospice and Palliative Medicine (n = 4678). The questions explored the language clinicians use for PS, and their experiences with PS. Nine hundred thirty-six (20% response rate) responded to the survey. About 83.21% preferred the terminology of PS compared with other terms. A majority felt that PS is a bioethically appropriate treatment for refractory physical and nonphysical symptoms in dying patients. Most felt PS was not an appropriate term in clinical scenarios when sedation occurred as an unintended side effect from standard treatments. Hospice clinicians use PS more consistently and with less distress than nonhospice clinician respondents. Benzodiazepines (63.1%) and barbiturates (18.9%) are most commonly prescribed for PS. PS is the preferred term among HPC clinicians for the proportionate use of pharmacotherapies to intentionally lower awareness for refractory symptoms in dying patients. PS is a bioethically appropriate treatment for refractory symptoms in dying patients. However, there is a lack of clear agreement about what is included in PS and how the practice of PS should be best delivered in different clinical scenarios. Future efforts to investigate PS should focus on describing the clinical scenarios in which PS is utilized and on the level of intended sedation necessary, in an effort to better unify the practice of PS.

Effect of Adjunctive Raloxifene Therapy on Severity of Refractory Schizophrenia in Women

A substantial proportion of women with schizophrenia experience debilitating treatment-refractory symptoms. The efficacy of estrogen in modulating brain function in schizophrenia has to be balanced against excess exposure of peripheral tissue. Raloxifene hydrochloride is a selective estrogen receptor modulator (mixed estrogen agonist/antagonist) with potential psychoprotective effects and fewer estrogenic adverse effects. To determine whether adjunctive raloxifene therapy reduces illness severity in women with refractory schizophrenia. This 12-week, double-blind, placebo-controlled, randomized clinical trial with fortnightly assessments was performed at an urban tertiary referral center and a regional center from January 1, 2006, to December 31, 2014. Participants included 56 women with schizophrenia or schizoaffective disorder and marked symptom severity despite substantial and stable antipsychotic doses. Data were analyzed using intention to treat as the basis. Adjunctive raloxifene hydrochloride, 120 mg/d, or placebo for 12 weeks. The primary outcome was the change in the Positive and Negative Syndrome Scale (PANSS) total score. Clinical response (defined as a ≥20% decrease in PANSS total score from baseline) and change in PANSS subscale scores, mood, cognition, reproductive hormone levels, and adverse events were also assessed. Of the 56 participants (mean [SD] age, 53 [7.7] years; age range, 40-70 years; mean [SD] duration of psychotic illness, 24 [11] years), 26 were randomized to raloxifene and 30 were randomized to placebo. Raloxifene produced a greater reduction in the PANSS total score relative to placebo (β = -6.37; 95% CI, -11.64 to -1.10; P = .02) and resulted in an increased probability of a clinical response (hazard ratio, 5.79; 95% CI, 1.46 to 22.97; P = .01). A significant reduction was found in the PANSS general symptom scores for the raloxifene compared with the placebo (β = -3.72; 95% CI, -6.83 to -0.61; P = .02) groups. For patients who completed the full 12-week trial, there was not a statistically significant treatment effect on PANSS positive symptom scores (β for change in raloxifene vs placebo, -1.92; 95% CI, -3.83 to 0.00; P = .05). Change in mood, cognition, and reproductive hormone levels and the rate of adverse events did not differ between groups. Raloxifene hydrochloride, 120 mg/d, reduces illness severity and increases the probability of a clinical response in women with refractory schizophrenia. This large trial of raloxifene in this patient population offers a promising, well-tolerated agent that has potential application in clinical practice. clinicaltrials.gov Identifier: NCT00361543.

Overactive bladder in children.

Overactive bladder (OAB) is a ubiquitous syndrome that is defined by urinary urgency with, or without urinary incontinence. OAB is observed in all parts of the world, with a prevalence of 5-12% in children (5-10 years of age) and a prevalence of 0.5% in older adolescents (16-18 years of age). Published data indicate that around a third of children with OAB are likely to become adults with similar complaints. Studies in children and in adults with OAB indicate that these individuals are more likely to also have anxiety, depression and attention deficit problems, and that appropriate treatment of these comorbidities can often improve the patient's OAB symptoms. Furthermore, data from twin studies and familial surveys seem to indicate a genetic component of OAB. Pharmacological treatments of OAB in children have improved in the past 5 years, moving beyond anticholinergic agents and including the off-label use of α-blockers, β3-agonists and intravesical botulinum toxin. Use of several different electrical stimulation techniques is also effective, both as first-line treatments, and for patients with treatment-refractory symptoms. Overall the outlook of children with OAB seems to be improving, with a greater understanding of the pathophysiology of this syndrome. Treatment modalities that target the source of the underlying problem, especially in children, are likely to provide the best patient outcomes.

Palliative sedation at a university palliative care unit--a descriptive analysis

Palliative sedation (pS) is indicated in the presence of end-stage disease with treatment-refractory symptoms not tolerable for the patient. We investigated the practice of pS at a university palliative care unit. Before starting pS the following data were documented: indication and decision making, type of sedation, life expectancy evaluated by the physician using the palliative prognostic index. Over the time of pS communication skills, depth of sedation, relief in symptoms, substitution of fluid and nutrition and used medications were collected. During evaluation time 99 patients died. 34 patients received pS (34 %). All patients suffered from cancer. Indications for palliative sedation were: terminal restlessness (56 %), dyspnea (39 %), pain (32 %), psychological distress (15 %), agitated delir (9 %), vomiting (3 %) and bleeding (3 %) (multiple nominations possible). In 31 cases (91 %) nurses were included for decision making. In 33 cases continuous sedation were initiated immediately (median duration 27.5 hours). The most applied medication was midazolam (94 %), sometimes combined with neuroleptics (44 %) and propofol (15 %). 91 % of the patients additionally received opioids. Artificial fluid was substituted in two cases. Palliative sedation started in the median 27.5 hours before death. The final physician assessment revealed complete symptom relief in 12 patients (35 %), very strong symptom relief in 20 patients (59 %) and moderate symptom relief in 2 patients (6 %). pS was successfully used as last resort for relief of treatment-refractory symptoms in one third of decedents at the investigated palliative care unit.

Controversies of the Effect of Ketamine on Cognition.

Controversies of the Effect of Ketamine on Cognition.