To combine or not to combine? A literature review of antidepressant combination therapy

OBJECTIVE: Treatment resistant depression is a common clinical problem and a major public health concern. The use of antidepressant combinations to overcome treatment resistance, while somewhat controversial, is a popular strategy in practice. This paper reviews published trials on combination antidepressants with a view to inform clinical practice. METHOD: A systematic but selective review of the published literature was conducted using EMBASE, PSYCHLIT and MEDLINE with relevant search terms. RESULTS: A number of trials suggesting efficacy of combination antidepressants were found. These are incorporated into a number of treatment guidelines for the management of treatment refractory depression. Clinicians should be cautious regarding pharmacokinetic and pharmacodynamic interactions, including the serotonin syndrome, however combination strategies are an effective option. CONCLUSIONS: Many antidepressants can be usefully combined especially if they engage separate mechanisms of action. Clinically, antidepressant combinations provide a useful resort in otherwise treatment resistant individuals. However, much further research is needed to determine relative efficacy and determine long term outcome.     

Does mindfulness training improve cognitive abilities? A systematic review of neuropsychological findings

Mindfulness meditation practices (MMPs) are a subgroup of meditation practices which are receiving growing attention. The present paper reviews current evidence about the effects of MMPs on objective measures of cognitive functions. Five databases were searched. Twenty three studies providing measures of attention, memory, executive functions and further miscellaneous measures of cognition were included. Fifteen were controlled or randomized controlled studies and 8 were case-control studies. Overall, reviewed studies suggested that early phases of mindfulness training, which are more concerned with the development of focused attention, could be associated with significant improvements in selective and executive attention whereas the following phases, which are characterized by an open monitoring of internal and external stimuli, could be mainly associated with improved unfocused sustained attention abilities. Additionally, MMPs could enhance working memory capacity and some executive functions. However, many of the included studies show methodological limitations and negative results have been reported as well, plausibly reflecting differences in study design, study duration and patients' populations. Accordingly, even though findings here reviewed provided preliminary evidence suggesting that MMPs could enhance cognitive functions, available evidence should be considered with caution and further high quality studies investigating more standardized mindfulness meditation programs are needed.     

To be or not to be a pro-T?

Recent studies have begun to unravel some of the molecular pathways that appear to control the processes of T cell determination in the earliest thymocyte precursors. In addition, the analyses of mouse mutants with an entirely alymphoid thymus have shed light on the developmental relationship of pro-T cells and thymic dendritic cells, revealing that development of thymocytes and thymic dendritic cells can be dissociated.     

Clinicians’ accounts of communication with patients in end-of-life care contexts: A systematic review

ObjectiveCommunication between patients and end-of-life care providers requires sensitivity given the context and complexity involved. This systematic review uses a narrative approach to synthesise clinicians’ understandings of communication in end-of-life care.MethodsA systematic, narrative synthesis approach was adopted given the heterogeneity across the 83 included studies. The review was registered prospectively on PROSPERO (ID: CRD42019125155). Medline was searched for all articles catalogued with the MeSH terms “palliative care,” “terminal care” or “end-of-life care,” and “communication”. Articles were assessed for quality using a modified JQI-QARI tool.ResultsThe findings highlight the centrality and complexity of communication in end-of-life care. The challenges identified by clinicians in relation to such communication include the development of skills necessary, complexity of interpersonal interactions, and ways in which organisational factors impact upon communication. Clinicians are also aware of the need to develop strategies for interdisciplinary teams to improve communication.ConclusionTraining needs for effective communication in end-of-life contexts are not currently being met.Practice ImplicationsClinicians need more training to address the lack of skills to overcome interactional difficulties. Attention is also needed to address issues in the organisational contexts in which such communication occurs.     

To disclose,or not to disclose? Context matters

Progress in understanding childhood disease using next-generation sequencing (NGS) portends vast improvements in the nature and quality of patient care. However, ethical questions surrounding the disclosure of incidental findings (IFs) persist, as NGS and other novel genomic technologies become the preferred tool for clinical genetic testing. Thus, the need for comprehensive management plans and multidisciplinary discussion on the return of IFs in pediatric research has never been more immediate. The aim of this study is to explore the views of investigators concerning the return of IFs in the pediatric oncology research context. Our findings reveal at least four contextual themes underlying the ethics of when, and how, IFs could be disclosed to participants and their families: clinical significance of the result, respect for individual, scope of professional responsibilities, and implications for the healthcare/research system. Moreover, the study proposes two action items toward anticipatory governance of IF in genetic research with children. The need to recognize the multiplicity of contextual factors in determining IF disclosure practices, particularly as NGS increasingly becomes a centerpiece in genetic research broadly, is heightened when children are involved. Sober thought should be given to the possibility of discovering IF, and to proactive discussions about disclosure considering the realities of young participants, their families, and the investigators who recruit them.     

The treatment of condylar fractures: to open or not to open? A critical review of this controversy

The treatment of condylar process fractures has generated a great deal of discussion and controversy in oral and maxillofacial trauma and there are many different methods to treat this injury. For each type of condylar fracture, the techniques must be chosen taking into consideration the presence of teeth, fracture height, patient's adaptation, patient's masticatory system, disturbance of occlusal function, deviation of the mandible, internal derangements of the temporomandibular Joint (TMJ) and ankylosis of the joint with resultant inability to move the jaw, all of which are sequelae of this injury. Many surgeons seem to favor closed treatment with maxillomandibular fixation (MMF), but in recent years, open treatment of condylar fractures with rigid internal fixation (RIF) has become more common. The objective of this review was to evaluate the main variables that determine the choice of method for treatment of condylar fractures: open or closed, pointing out their indications, contra-indications, advantages and disadvantages.     

Regulatory development of geriatric medicines: To GIP or not to GIP?

Geriatric patients represent the main users of medicines, but are historically often minimally included in clinical trials, resulting in a gap in the knowledge of the benefit/risk balance of medicines in this heterogeneous population. As the worldwide population is aging, the need for safe and effective medicines for older patients is proportionally increasing. The aim of this review is to provide an overview of the current regulatory status of the development of geriatric medicines, the encountered challenges and the view of the involved stakeholders, coming to the conclusion whether it is necessary or not to implement a Geriatric Investigation Plan (GIP), by analogy with pediatrics.     

Aspergillus detection in airways of ICU COVID-19 patients: To treat or not to treat?

It is now well known that patients with severe COVID-19 are at risk for developing invasive pulmonary aspergillosis (IPA). Nevertheless, the symptomatology of IPA is often atypical in mechanically ventilated patients and the radiological aspects of SARS CoV-2 pneumonia and IPA are difficult to differentiate. In this context, the significance of the presence of Aspergillus in respiratory tract samples (detected by culture, galactomannan antigen, or specific PCR) is not yet fully understood. Here we report two cases of intubated and mechanically ventilated ICU patients with SARS-CoV-2 pneumonia, in whom Aspergillus was detected in respiratory samples, who had a favorable outcome in the absence of antifungal treatment. These two cases highlight the difficulty of using the new definitions of COVID-19 associated pulmonary aspergillosis for routine management of patients.     

Does neurocognitive functioning predict future or persistence of ADHD? A systematic review

Many children with ADHD remain symptomatic in (young) adulthood. It is important to understand what characterizes this persistent ADHD group. Since ADHD has been associated with neurocognitive dysfunctioning on a variety of neurocognitive domains, and many of these domains are influenced by the same risk genes that influence ADHD, neurocognitive functions are a potential predictor for ADHD persistence. We carried out a systematic literature review on the predictive value of neurocognitive functioning for future ADHD. Based on eighteen studies there was no evidence that either automatically controlled (requiring little mental effort; lower level), or more consciously controlled (requiring high levels of mental effort; higher level) neurocognitive functions differentiated ADHD persistence from remittance. In general, both persisters and remitters showed weaker performance than typically developing controls, although the effect was smaller for remitters. Neurocognitive functions measured in childhood predicted ADHD a few years later, regardless of the type of neurocognitive function. Our findings do not support the model of Halperin and Schulz (2006), which suggests a maturation of more consciously controlled neurocognitive functions in ADHD remitters.     

To blastocyst or not to blastocyst? That is the question

Recent advances in culture media preparations have allowed for cleavage embryos to be developed to the blastocyst stage. Blastocysts are regarded as having increased implantation potential, and two blastocysts are typically transferred, which reduces the occurrence of high order multiple gestations. However, with current techniques, most cleavage embryos do not become blastocysts and it is not clear how many of these embryos would have implanted had they been replaced at the cleavage stage. Furthermore, experience with blastocyst cryopreservation is lacking and the overall benefit of blastocyst culture is unknown, unless we consider the combined pregnancy rates of both fresh and frozen blastocysts.