Safe and effective sofosbuvir-based therapy in patients with mental health disease on hepatitis C virus treatment

AIMTo study impact of baseline mental health disease on hepatitis C virus (HCV) treatment; and Beck’s Depression Inventory (BDI) changes with sofosbuvir- and interferon-based therapy. METHODSThis is a retrospective cohort study of participants from 5 studies enrolled from single center trials conducted at the Clinical Research Center of the National Institutes of Health, Bethesda, MD, United States. All participants were adults with chronic HCV genotype 1 infection and naïve to HCV therapy. Two of the studies included HCV mono-infected participants only (SPARE, SYNERGY-A), and 3 included human immunodeficiency virus (HIV)/HCV co-infected participants only (ERADICATE, PFINPK, and ALBIN). Patients were treated for HCV with 3 different regimens: Sofosbuvir and ribavirin in the SPARE trial, ledipasvir and sofosbuvir in SYNERGY-A and ERADICATE trials, and pegylated interferon (IFN) and ribavirin for 48 wk in the PIFNPK and ALBIN trials. Participants with baseline mental health disease (MHD) were identified (defined as either a DSM IV diagnosis of major depression, bipolar disorder, schizophrenia, generalized anxiety, and post-traumatic stress disorder or requiring anti-depressants, antipsychotics, mood stabilizers or psychotropics prescribed by a psychiatrist). For our first aim, we compared sustained virologic response (SVR) and adherence (pill counts, study visits, and in 25 patients, blood levels of the sofosbuvir metabolite, GS-331007) within each study. For our second aim, only patients with HIV coinfection were evaluated. BDI scores were obtained pre-treatment, during treatment, and post-treatment among participants treated with sofosbuvir-based therapy, and compared to scores from participants treated with interferon-based therapy. Statistical differences for both aims were analyzed by Fisher’s Exact, and t-test with significance defined as a P value less than 0.05. RESULTSBaseline characteristics did not differ significantly between all participants with and without MHD groups treated with sofosbuvir-based therapy. Among patients treated with sofosbuvir-based therapy, the percentage of patients with MHD who achieved SVR was the same as those without (SPARE: 60.9% of those MHD compared to 67.6% in those without, P = 0.78; SYNERGY-A: 100% of both groups; ERADICATE: 100% compared to 97.1%). There was no statistically significant difference in pill counts, adherence to study visits between groups, nor mean serum concentrations of GS-331007 for each group at week 2 of treatment (P = 0.72). Among patients with HIV co-infection, pre-treatment BDI scores were similar among patients treated with sofosbuvir, and those treated with interferon (sofosbuvir-based 5.24, IFN-based 6.96; P = 0.14); however, a dichotomous effect on was observed during treatment. Among participants treated with directly acting antiviral (DAA)-based therapy, mean BDI scores decreased from 5.24 (pre-treatment) to 3.28 during treatment (1.96 decrease, P = 0.0034) and 2.82 post-treatment. The decrease in mean score from pre- to post-treatment was statistically significant (-2.42, P = 0.0012). Among participants treated with IFN-based therapy, mean BDI score increased from 6.96 at pre-treatment to 9.19 during treatment (an increase of 2.46 points, P = 0.1), and then decreased back to baseline post-treatment (mean BDI score 6.3, P = 0.54). Overall change in mean BDI scores from pre-treatment to during treatment among participants treated with DAA-based and IFN-therapy was statistically significant (-1.96 and +2.23, respectively; P = 0.0032). This change remained statistically significant when analysis was restricted to participants who achieved SVR (-2.0 and +4.36, respectively; P = 0.0004). CONCLUSIONSofosbuvir-based therapy is safe and well tolerated in patients with MHD. A decline in BDI associated with sofosbuvir-based HCV treatment suggests additional MHD benefits, although the duration of these effects is unknown.

Recent advances in anxiety disorders:Focus on animal models and pathological mechanisms

Anxiety disorders have become one of the most severe psychiatric disorders,and the incidence is increasing every year.They impose an extraordinary personal and socioeconomic burden.Anxiety disorders are influenced by multiple complex and interacting genetic,psychological,social,and environmental factors,which contribute to disruption or imbalance in homeostasis and eventually cause pathologic anxiety.The selection of a suitable animal model is important for the exploration of disease etiology and pathophysiology,and the development of new drugs.Therefore,a more comprehensive understanding of the advantages and limitations of existing animal models of anxiety disorders is helpful to further study the underlying pathological mechanisms of the disease.This review summarizes animal models and the pathogenesis of anxiety disorders,and discusses the current research status to provide insights for further study of anxiety disorders.

The Scientific Evidence That Today’s Psychiatry Cripples Itself—By Excluding‘Intent’

PSYCHIATRISTS DISAGREE profoundly with lawyers,about what we human beings are capable of.The one says we have‘intent’—the other that we do not.They cannot both be right.All non-psychiatrist doctors must perforce agree with the lawyers.This paper argues that these harmful discrepancies will continue,until we undo the separate watertight human knowledge silos,which have grown up between legal procedures,general medicine,and psychiatric practice.All three would benefit.Psychiatry in particular,suffers from a grievously narrow view of scientific evidence,one which is open to fundamental criticism.There are radical differences in how the fuzzy concept of‘intent’is regarded in law,in general clinical medicine and in psychiatry.Once‘intent’is accorded its due weight,our understanding of justice,health and sanity is vastly improved,allowing us hugely more optimism.This paper is based on two earlier papers—The Scientific Evidence That‘Intent’Is Vital for Healthcare and Why Quakerism Is More Scientific Than Einstein.These are deployed here,to unpick the unhealthy tangle in which today’s psychiatry now finds itself.Its six sections are—(1)why‘intent’matters in law,in medicine&in psychiatry;(2)scientific quagmires;(3)a working definition for‘madness’;(4)“children are impressionable”;(5)“trust me,I’m a doctor”;and(6)skin heals,why can’t minds?The breakthrough is that verbal fuzziness means that words can mean different things at different times––not that they are 100%meaningless.Only a better understanding of trust,autonomy and consent can open the way to something that is painfully absent from today’s psychiatry––a cure for any and all mental disease.

Caring for Mental Disease

Government increases the funding for treating the mentally ill following cases of uncontrollable violence The Ministry of Health plans to renovate or expand 550 psychiatric hospitals and psychiatric

Remote multi‐wave radioneuroengineering:An innovative technology for non‐contact radio restoration of damaged nervous tissue of the human brain and spinal cord

Objectives: Significant advances in neurosciences will result from research focused on the non‐contact treatment of the nervous tissue(NT).The objective of the article is to describe a novel non‐contact method of restoration of damaged NT of the human brain and spinal cord that was termed multi‐wave neuro‐bioengineering. Methods: The method includes a purposeful complex program of different therapeutic ionizing and non‐ionizing electromagnetic radiation effects on the damaged NT,which is approved for clinical practice. Exposure of the human brain to a stepwise algorithmized combination of different ionizing and non‐ionizing radiations and simultaneous application of various types of electromagnetic radiation at the specific site of restoration considerably reduce the adverse effects of all types of radiation on NT.Results: The technology for non‐contact restoration of the injured tissue of brain or spinal cord was appiled in 30 cases of neurological disorders using the stereotaxic system, structural resonance therapy, radiotherapy and focused ultrasound. The applied methods are approved for humans and theor programmed combination opens new perspective for the treatment of brain and spinal cord disorders. Conclusions: The approach provides quick restoration of the disordered function of damaged brain tissue and establishes a new paradigm of radio non‐contact neurorestoration of the brain and spinal cord.