Gene therapy in osteoarticular diseases: where are we?

Elucidation of the molecular and cellular basis of joint destruction in rheumatoid arthritis is revealing novel targets for gene transfer therapy of this disease. A recent meeting³ evaluated progress in gene delivery systems and discussed future strategies.     

Does music therapy enhance behavioral and cognitive function in elderly dementia patients? A systematic review and meta-analysis

Demographic aging is a worldwide phenomenon, cognitive and behavioral impairment is becoming global burden of nerve damage. However, the effect of pharmacological treatment is not satisfying. Therefore, we analyzed the efficacy of music therapy in elderly dementia patients, and if so, whether music therapy can be used as first-line non-pharmacological treatment. A comprehensive literature search was performed on PubMed, EMbase and the Cochrane Library from inception to September 2016. A total of 34 studies (42 analyses, 1757 subjects) were included; all of them had an acceptable quality based on the PEDro and CASP scale scores. Studies based on any type of dementia patient were combined and analyzed by subgroup. The standardized mean difference was −0.42 (-0.74 to −0.11) for disruptive behavior and 0.20 (-0.09 to 0.49) for cognitive function as primary outcomes in random effect models using controls as the comparator; the secondary outcomes were depressive score, anxiety and quality of life. No evidence of publication bias was found based on Begg’s and Egger’s test. The meta-analysis confirmed that the baseline differences between the two groups were balanced. Subgroup analyses showed that disease sub-type, intervention method, comparator, subject location, trial design, trial period and outcome measure instrument made little difference in outcomes. The meta-regression may have identified the causes of heterogeneity as the intervention method, comparator and trial design. Music therapy was effective when patients received interactive therapy with a compared group. There was positive evidence to support the use of music therapy to treat disruptive behavior and anxiety; there were positive trends supporting the use of music therapy for the treatment of cognitive function, depression and quality of life. This study is registered with PROSPERO, number CRD42016036153.     

Microbiome studies in urology- where do we stand and where can we reach?

The role of microbiome milieu in the urinary tract, their interplay in diverse urological conditions and their therapeutic implications are not completely understood. The microbiome has contributed towards urinary tract infections, urolithiasis and urological cancers. The possibility of manipulating microbiome for diagnosis and treatment is evolving. Probiotics might help in overcoming the problems of recurrent infection and antibiotic resistance. Novel applications like stents and catheters coated with non-pathogenic organisms are being developed. Research in the urinary microbiome has progressed from using mouse models to the presently available three- dimensional cultured organoids, thus making it more feasible. As our knowledge regarding the urinary microbiome increases, justice can be done to many patients in whom the advancements can be used for prophylaxis, diagnosis, treatment and even in improving their quality of life. The growing amount of antibiotic resistance is also a matter of concern and probiotics might be the answer to this upcoming calamity. In this review, we have discussed the role of the urinary microbiome in pathogenesis, diagnosis and treatment of urological conditions and pondered upon its future prospects.     

Gene therapy strategies: can we eradicate HIV?

Despite the tremendous advances in antiretroviral combination therapy over the last decade, eradication of HIV from the infected organism is still an elusive goal. Lifelong therapy is associated with potential long-term toxicity, adherence problems, and development of drug resistance. Thus, gene therapy approaches targeting viral eradication are still attractive. Here a number of studies have failed to show a clear clinical benefit yet. Current approaches were mainly limited by a low number of transduced cells and genotoxicity. The use of new vector systems and the right choice of target cells and improved transduction protocols may overcome these obstacles. Recent reports on the use of newly developed transgenes either allowing for an enrichment of transduced cells by an in vivo selection advantage or restoration of a functional immune system which is resistant to HIV infection nourished the hope for continuous progress in this field. Indeed the intriguing finding that HIV seems to be eradicated in an individual case study after stem cell transplantation with a mutant coreceptor (CCR5 delta 32 deletion) underlines the proof of the concept.     

Do we need to challenge thoughts in cognitive behavior therapy?

Cognitive behavior therapy (CBT) emphasizes the primacy of cognition in mediating psychological disorder. It aims to alleviate distress by modifying cognitive content and process, realigning thinking with reality. Recently, various authors have questioned the need for CBT therapists to use logico-rational strategies to directly challenge maladaptive thoughts. Hayes [Hayes, S.C. (2004). Acceptance and commitment therapy and the new behavior therapies. In S.C. Hayes, V.M. Follette, & M.M. Linehan (Eds.), Mindfulness and acceptance: Expanding the cognitive behavioral tradition. (pp. 1-29). New York: Guilford] has identified three empirical anomalies in the research literature. Firstly, treatment component analyzes have failed to show that cognitive interventions provide significant added value to the therapy. Secondly, CBT treatments have been associated with a rapid symptomatic improvement prior to the introduction of specific cognitive interventions. Thirdly, there is a paucity of data that changes in cognitive mediators instigate symptomatic change. This paper critically reviews the empirical literature that addresses these significant challenges to CBT. A comprehensive review of component studies finds little evidence that specific cognitive interventions significantly increase the effectiveness of the therapy. Although evidence for the early rapid response phenomenon is lacking, there is little empirical support for the role of cognitive change as causal in the symptomatic improvements achieved in CBT. These findings are discussed with reference to the key question: Do we need to challenge thoughts in CBT?     

Are exposure-based cognitive behavioral therapies safe during pregnancy?

Anxiety disorders during pregnancy are highly prevalent and associated with serious and enduring consequences for both mother and child. Exposure-based cognitive behavioral (CBT) and behavioral therapies (BT) represent the most empirically supported psychosocial treatments for anxiety disorders in general adult samples. Pregnant women, however, generally have been excluded from this body of research. Evidence that pregnant women inhabit a unique biological context combined with untested assumptions that exposure would unduly stress or harm the fetus have likely prohibited inquiry. This paper seeks to remedy this gap by integrating findings from obstetric, psychiatric, and psychological research to inform central questions regarding exposure-based treatment of anxiety disorders during pregnancy. Based on available evidence, we consider the potential risks and benefits of CBT/BT for anxiety disorders during pregnancy relative to other currently available treatment options. From a multidisciplinary research perspective, we argue that exposure-based therapies are likely to be safe during pregnancy, particularly relative to the alternatives. However, we also highlight critical questions for future research to directly test the biopsychological impact of exposure-based therapies among pregnant women.     

Does the addition of cognitive behavioral therapy improve panic disorder treatment outcome relative to medication alone in the primary-care setting?

BACKGROUND: Randomized clinical trials indicate a benefit from combining medications with cognitive behavioral therapy (CBT) relative to medication alone for panic disorder. Using an as-treated analysis, we evaluated whether the addition of CBT enhanced outcomes for panic disorder relative to medications alone in the primary-care setting. METHOD: Primary-care patients with panic disorder reported on their receipt of CBT and medications over the 3 months following baseline assessment. The degree to which outcomes for those who used anti-panic medications were enhanced by the receipt of at least one component of CBT was analyzed using a propensity score model that took into account observable baseline patient characteristics influencing both treatment selection and outcomes. RESULTS: The addition of CBT resulted in statistically and clinically significant improvements at 3 months on anxiety sensitivity, social avoidance, and disability. Also, patients receiving CBT in the first 3 months of the study were more improved at 12 months than patients who took medications only during the first 3 months of the study. CONCLUSIONS: The clinical utility of the findings are discussed in terms of the importance of primary-care physicians encouraging their panic disorder patients to receive CBT as well as medications.     

Pancreatic cancer genomics: where can the science take us?

The incidence of pancreatic ductal adenocarcinoma (PDAC) is steadily increasing and the annual death‐to‐incidence ratio approaches one. This is a figure that has not changed for several decades. Surgery remains the only chance of cure; however, only less than 20% of patients are amenable to operative resection. Despite successful surgical resection, the majority of the patients still succumb to recurrent metastatic disease. Therefore, there is an urgent need to develop novel therapeutic strategies and to better select patients for current therapies. In this review, we will discuss current management by highlighting the landmark clinical trials that have shaped current care. We will then discuss the challenges of therapeutic development using the current randomized‐controlled trial paradigm when confronted with the molecular heterogeneity of PDAC. Finally, we will discuss strategies that may help to shape the management of PDAC in the near future.     

Bipolar disorder: what can psychotherapists learn from the cognitive research?

Randomized controlled trials of psychological treatment, principally cognitive therapy, for bipolar disorder have yielded inconsistent results. Given the status of this evidentiary base, we provide a more fine-grained analysis of the cognitive profiles associated with bipolar disorder to inform clinical practice. In this practice-friendly review, we consider evidence that both negative and positive cognitive styles are related to bipolar disorder. Cross-sectional and prospective evidence suggest that negative cognitive styles are related to depression within bipolar disorder, but there also is evidence that bipolar disorder is related to an elevated focus on goals as well as to increases in confidence during manic states. With such findings as backdrop, we consider the outcomes of psychological treatments for bipolar disorder and advance several suggestions for clinical practice.     

An open trial with cognitive behavioral therapy for blood- and injection phobia in pregnant women—a group intervention program

Around 7% of pregnant women suffer from blood- and injection phobia. The aim was to investigate if cognitive behavior group therapy (CBT) is effective in treating pregnant women’s blood- and injection phobia. Thirty pregnant women with blood- and injection phobia according to DSM-IV took part in an open treatment intervention. A two-session cognitive behavior group therapy was conducted. As controls, 46 pregnant women with untreated blood- and injection phobia and 70 healthy pregnant women were used. Repeated measures ANOVA were performed. The scores for the CBT treatment group on the “Injection Phobia Scale-Anxiety” were reduced both after each treatment session and postpartum (p < 0.001). Anxiety and depressive symptoms were also reduced (p < 0.001). Cognitive-behavior group therapy for pregnant women with blood- and injection phobia is effective and stable up to at least 3 months postpartum. It seems also to reduce anxiety and depressive symptoms during pregnancy.     

Stem cells for neurodegenerative disorders: where can we go from here?

The use of stem cells in cell replacement therapy for neurodegenerative diseases has received a great deal of scientific and public interest in recent years. This is due to the remarkable pace at which paradigm-changing discoveries have been made regarding the neurogenic potential of embryonic, fetal, and adult cells. Over the last decade, clinical fetal tissue transplants have demonstrated that dopaminergic neurons can survive long term and provide functional clinical benefits for patients with Parkinson's disease. Pluripotent embryonic stem cells and multipotent neural stem cells may provide renewable sources that could replace these primary fetal grafts. Considerable advancement has been made in generating cultures with high numbers of neurons in general and of dopaminergic neurons using a varied array of techniques. However, much of this encouraging progress still remains to be tested on long-term expanded human cultures. Further problems include the low survival rate of these cells following transplantation and the tumorigenic tendencies of embryo-derived cells. However, pre-differentiation or genetic modification of stem cell cultures prior to transplantation may help lead to the generation of high numbers of cells of the desired phenotype following grafting. Boosting particular factors or substrates in the culture media may also protect grafted neurons from oxidative and metabolic stress, and provide epigenetic trophic support. Possible endogenous sources of cells for brain repair include the transdifferentiation of various types of adult cells into neurons. Despite the excitement generated by examples of this phenomenon, further work is needed in order to identify the precise instructive cues that generate neural cells from many other tissue types, and whether or not the new cells are functionally normal. Furthermore, issues such as cell homogeneity and fusion need to be addressed further before the true potential of transdifferentiation can be known. Endogenous stem cells also reside in the neurogenic zones of the adult brain (ventricle lining and hippocampus). Further elucidation of the mechanisms that stimulate cell division and migration are required in order to learn how to amplify the small amount of new cells generated by the adult brain and to direct these cells to areas of injury or degeneration. Finally, a more fundamental understanding of brain injury and disease is required in order to circumvent local brain environmental restrictions on endogenous cell differentiation and survival.