Paliperidone extended-release: does it have a place in antipsychotic therapy?

Paliperidone (9-hydroxy-risperidone), the active metabolite of risperidone, was approved for treating schizophrenia worldwide in 2006 as paliperidone extended-release (PER), and became the first second-generation antipsychotic specifically licensed for treating schizoaffective disorder in 2009. However, at the same time, its comparatively high cost gave rise to concerns about the cost-effectiveness of PER as compared with its precursor, risperidone. This paper reviews the existing knowledge of the pharmacology, kinetics, efficacy, tolerability, and fields of application of PER, and compares PER with risperidone in order to determine whether it has a place in antipsychotic therapy. An independent assessment of all relevant publications on PER published until July 2010 was undertaken. PER has a unique pharmacological profile, including single dosing, predominantly renal excretion, low drug–drug interaction risk, and differs from risperidone in terms of mode of action and pharmacokinetics. High-level evidence suggests that PER is efficacious and safe in schizophrenia, schizoaffective disorder, and acute manic episodes. There is a striking lack of published head-to-head comparisons between PER and risperidone, irrespective of indication. Low-level evidence shows a lower risk for hyperprolactinemia and higher patient satisfaction with PER than with risperidone. PER adds to the still limited arsenal of second-generation antipsychotics. In the absence of direct comparisons with risperidone, it remains difficult to come to a final verdict on the potential additional therapeutic benefits of PER which would justify its substantially higher costs as compared with risperidone. However, in terms of pharmacology, the available evidence cautiously suggests a place for PER in modern antipsychotic therapy

An international study of the prevalence of substance use in patients with delusional infestation

To the Editor: Delusional infestation (DI) is a disorder characterised by the belief of being infested with living organisms or objects.1 Insects and worms are the most common concerns. Objects, such as fibers or threads, are increasingly reported by patients. DI can be primary or secondary to mental illness, physical illness, prescribed medication, and misuse of substances such as amphetamines, cannabis, codeine, cocaine, or opiates. Dermatologists are usually the specialists to whom a patient with DI is referred because patients believe that they have primarily a skin diseas

Tomophobia, the phobic fear caused by an invasive medical procedure - an emerging anxiety disorder: a case report

<p>Abstract</p> <p>Introduction</p> <p>Tomophobia refers to fear or anxiety caused by forthcoming surgical procedures and/or medical interventions.</p> <p>Case presentation</p> <p>We present the case of a 69-year-old Caucasian man who refused urgently indicated medical intervention because of severe tomophobia.</p> <p>Conclusion</p> <p>Due to the rising number of surgical interventions in modern medicine, as well as the high number of unrecognised cases of tomophobia, this common but underdiagnosed anxiety disorder should be highlighted.</p

HLA Ligand Atlas: a benign reference of HLA-presented peptides to improve T-cell-based cancer immunotherapy

BACKGROUND The human leucocyte antigen (HLA) complex controls adaptive immunity by presenting defined fractions of the intracellular and extracellular protein content to immune cells. Understanding the benign HLA ligand repertoire is a prerequisite to define safe T-cell-based immunotherapies against cancer. Due to the poor availability of benign tissues, if available, normal tissue adjacent to the tumor has been used as a benign surrogate when defining tumor-associated antigens. However, this comparison has proven to be insufficient and even resulted in lethal outcomes. In order to match the tumor immunopeptidome with an equivalent counterpart, we created the HLA Ligand Atlas, the first extensive collection of paired HLA-I and HLA-II immunopeptidomes from 227 benign human tissue samples. This dataset facilitates a balanced comparison between tumor and benign tissues on HLA ligand level. METHODS Human tissue samples were obtained from 16 subjects at autopsy, five thymus samples and two ovary samples originating from living donors. HLA ligands were isolated via immunoaffinity purification and analyzed in over 1200 liquid chromatography mass spectrometry runs. Experimentally and computationally reproducible protocols were employed for data acquisition and processing. RESULTS The initial release covers 51 HLA-I and 86 HLA-II allotypes presenting 90,428 HLA-I- and 142,625 HLA-II ligands. The HLA allotypes are representative for the world population. We observe that immunopeptidomes differ considerably between tissues and individuals on source protein and HLA-ligand level. Moreover, we discover 1407 HLA-I ligands from non-canonical genomic regions. Such peptides were previously described in tumors, peripheral blood mononuclear cells (PBMCs), healthy lung tissues and cell lines. In a case study in glioblastoma, we show that potential on-target off-tumor adverse events in immunotherapy can be avoided by comparing tumor immunopeptidomes to the provided multi-tissue reference. CONCLUSION Given that T-cell-based immunotherapies, such as CAR-T cells, affinity-enhanced T cell transfer, cancer vaccines and immune checkpoint inhibition, have significant side effects, the HLA Ligand Atlas is the first step toward defining tumor-associated targets with an improved safety profile. The resource provides insights into basic and applied immune-associated questions in the context of cancer immunotherapy, infection, transplantation, allergy and autoimmunity. It is publicly available and can be browsed in an easy-to-use web interface at https://hla-ligand-atlas.org

Delusional Infestation

Summary: This papers aims at familiarizing psychiatric and nonpsychiatric readers with delusional infestation (DI), also known as delusional parasitosis. It is characterized by the fixed belief of being infested with pathogens against all medical evidence. DI is no single disorder but can occur as a delusional disorder of the somatic type (primary DI) or secondary to numerous other conditions. A set of minimal diagnostic criteria and a classification are provided. Patients with DI pose a truly interdisciplinary problem to the medical system. They avoid psychiatrists and consult dermatologists, microbiologists, or general practitioners but often lose faith in professional medicine. Epidemiology and history suggest that the imaginary pathogens change constantly, while the delusional theme “infestation” is stable and ubiquitous. Patients with self-diagnosed “Morgellons disease” can be seen as a variation of this delusional theme. For clinicians, clinical pathways for efficient diagnostics and etiology-specific treatment are provided. Specialized outpatient clinics in dermatology with a liaison psychiatrist are theoretically best placed to provide care. The most intricate problem is to engage patients in psychiatric therapy. In primary DI, antipsychotics are the treatment of choice, according to limited but sufficient evidence. Pimozide is no longer the treatment of choice for reasons of drug safety. Future research should focus on pathophysiology and the neural basis of DI, as well as on conclusive clinical trials, which are widely lacking. Innovative approaches will be needed, since otherwise patients are unlikely to adhere to any study protocol