Quality and denoising in real‐time functional magnetic resonance imaging neurofeedback: A methods review

Neurofeedback training using real‐time functional magnetic resonance imaging (rtfMRI‐NF) allows subjects voluntary control of localised and distributed brain activity. It has sparked increased interest as a promising non‐invasive treatment option in neuropsychiatric and neurocognitive disorders, although its efficacy and clinical significance are yet to be determined. In this work, we present the first extensive review of acquisition, processing and quality control methods available to improve the quality of the neurofeedback signal. Furthermore, we investigate the state of denoising and quality control practices in 128 recently published rtfMRI‐NF studies. We found: (a) that less than a third of the studies reported implementing standard real‐time fMRI denoising steps, (b) significant room for improvement with regards to methods reporting and (c) the need for methodological studies quantifying and comparing the contribution of denoising steps to the neurofeedback signal quality. Advances in rtfMRI‐NF research depend on reproducibility of methods and results. Notably, a systematic effort is needed to build up evidence that disentangles the various mechanisms influencing neurofeedback effects. To this end, we recommend that future rtfMRI‐NF studies: (a) report implementation of a set of standard real‐time fMRI denoising steps according to a proposed COBIDAS‐style checklist ( https://osf.io/kjwhf/ ), (b) ensure the quality of the neurofeedback signal by calculating and reporting community‐informed quality metrics and applying offline control checks and (c) strive to adopt transparent principles in the form of methods and data sharing and support of open‐source rtfMRI‐NF software. Code and data for reproducibility, as well as an interactive environment to explore the study data, can be accessed at https://github.com/jsheunis/quality‐and‐denoising‐in‐rtfmri‐nf.     

Translational development of splice-modifying antisense oligomers

Introduction: Antisense nucleic acid analogues can interact with pre-mRNA motifs and influence exon or splice site selection and thereby alter gene expression. Design of antisense molecules to target specific motifs can result in either exon exclusion or exon inclusion during splicing. Novel drugs exploiting the antisense concept are targeting rare, life-limiting diseases; however, the potential exists to treat a wide range of conditions by antisense-mediated splice intervention.

Areas covered: In this review, the authors discuss the clinical translation of novel molecular therapeutics to address the fatal neuromuscular disorders Duchenne muscular dystrophy and spinal muscular atrophy. The review also highlights difficulties posed by issues pertaining to restricted participant numbers, variable phenotype and disease progression, and the identification and validation of study endpoints.

Expert opinion: Translation of novel therapeutics for Duchenne muscular dystrophy and spinal muscular atrophy has been greatly advanced by multidisciplinary research, academic-industry partnerships and in particular, the engagement and support of the patient community. Sponsors, supporters and regulators are cooperating to deliver new drugs and identify and define meaningful outcome measures. Non-conventional and adaptive trial design could be particularly suited to clinical evaluation of novel therapeutics and strategies to treat serious, rare diseases that may be problematic to study using more conventional clinical trial structures.     

Sudden infant death syndrome and diphtheria-tetanus-pertussis-poliomyelitis vaccination status

Summary— Because diphtheria, tetanus, pertussis and poliomyelitis vaccine is routinely given during the period of highest incidence of sudden infant death syndrome (SIDS), we carried out a retrospective case-control study to assess whether such vaccination increased the risk of SIDS. The vaccination status of 118 SIDS and 332 control children, matched for sex, date of birth and age of the victims at death, was compared: the victims of SIDS were not significantly more often vaccinated than control children, the odds ratio was estimated at 1.9 with a 95% confidence interval from 0.9 to 3.9. There was a statistical difference between vaccination status of SIDS cases and controls aged less than three months. Nine percent of SIDS cases under 3 months had been vaccinated whereas the matched controls had not. In our study DTCP vaccination was not a risk factor for SIDS; although more of the SIDS infants less than 3 months of age had been vaccinated. This result however, concerns only one subgroup of the population studied and needs to be confirmed with another study of only SIDS infants less than 3 months of age, because DTCP vaccination was not a risk factor for SIDS when considering the total sample of the study.     

Care related pain in hospitalized patients: A cross‐sectional study

Context: Care‐related pain includes pain occurring during transportation, movement, diagnostic imaging, physical examination, or treatment. Its prevalence has never been assessed in a large adult inpatient population. Objective: To identify the procedures likely to induce or increase pain in hospital patients, attempting to separate the most painful from those reported as most frequently inducing pain. Design: A single‐day cross‐sectional survey conducted in two large French teaching hospitals, including all hospitalized patients, free of communication problems. One third was randomly selected and interviewed about the painful episodes that had occurred or were associated with the procedures performed during the previous two weeks. Patients were interviewed using a structured questionnaire. Results: Six‐hundred‐eighty‐four patients were randomly selected. Six‐hundred‐seventy‐one painful events were reported in 55% of the patients, with an average of 1.8events/patient. Fifty‐two percent of the painful events were associated with procedures performed by non‐medical staff; 38% of the painful episodes occurred during procedures involving vascular puncture and 24% during patients’ mobilization. In 57% of painful procedures, pain was rated as severe or extremely severe. The most painful procedures were invasive procedures, other than vascular and non vascular punctures (74% of severe and extremely severe painful episodes). Maximum pain intensity was rated higher for procedures that were repeated than for those experienced only once (62% versus 53%, p=0.02). Conclusion: This survey gives new insight into our daily practice. Proper management of care‐related pain should be a major concern of all hospital staff to improve the quality of our health care.