Ivy leaf dry extract EA 575 for the treatment of acute and chronic cough in pediatric patients: review and expert survey.

OBJECTIVES: EA 575 (Prospan) is a herbal medicine containing a dried extract of ivy leaves (drug extract ratio 5-7.5:1; extraction solvent, 30% ethanol). Although widely used for the treatment of cough, there remains a lack of clarity on the effects of EA 575 in children. This study aimed to evaluate the efficacy and tolerability of EA 575 in pediatric patients with cough, via a literature review and expert survey. METHODS: A MEDLINE/PubMed database search was performed to identify articles evaluating the efficacy and tolerability of EA 575 in pediatric patients with cough. An online survey of international pediatric cough experts was conducted to gather expert opinion regarding the use of EA 575 for pediatric cough. RESULTS: Ten controlled clinical trials and nine observational studies were identified. Controlled trials reported improvements in lung function and subjective cough symptoms with EA 575, while observational studies indicated overall favorable efficacy. EA 575 was generally well tolerated, with a low incidence of adverse events in children of all ages, including those aged <1 year. Survey responses from ten experts aligned with findings from the reviewed studies. Most experts agreed that EA 575 may improve quality of life, and highlighted its potential benefits on sleep. CONCLUSIONS: EA 575 has minimal side effects in pediatric patients with cough, as demonstrated by large, real-world studies. EA 575 may provide clinical benefits in pediatric patients; however, more robust clinical trials are needed to confirm its efficacy.

EA 575 (Prospan) is a medicine containing a dried extract of ivy leaves that is used to treat coughs. The aim of this review was to evaluate the available published information on the health benefits and side effects of EA 575 in children with coughs. We also conducted a survey of doctors who treat children with coughs. We found information from ten research trials that compared EA 575 with another cough medicine or a "dummy medicine". Although these studies included only a small number of children, the results suggested that children's breathing and cough symptoms may improve with EA 575 treatment. We also found nine studies that included children being treated in normal clinical situations and not in a research setting. Most of the children included in these studies and their doctors thought that EA 575 treatment was beneficial. A low number of side effects was reported in children of all ages, including in infants aged <1 year. Survey responses from ten doctors generally agreed with the findings from the research studies. Most of the doctors thought that EA 575 may improve quality of life. Improved sleep was commonly mentioned by doctors. Overall, our findings indicate that EA 575 has minimal side effects in children; we call for more research on the benefits of EA 575 on cough symptoms in children.

Therapeutic principles and unmet needs in the treatment of cough in pediatric patients: review and expert survey.

BACKGROUND: There are evidence gaps in the management of pediatric cough, particularly for acute pediatric cough. This study had two aims: to identify therapeutic principles and unmet needs in the treatment of cough in pediatric patients (internationally), and to consider the evidence required to address these unmet needs. METHODS: A MEDLINE/PubMed database search was performed to identify articles describing therapeutic principles in the treatment of pediatric cough. An online survey of international pediatric cough experts was conducted, with questions on the definitions, diagnosis, treatment, and unmet needs in pediatric cough management. RESULTS: Cough guidelines have differing definitions of pediatric patients (≤12-18 years), acute pediatric cough (< 2-3 weeks), and chronic pediatric cough (> 4-8 weeks). Similarly, among 18 experts surveyed, definitions varied for pediatric patients (≤10-21 years), acute pediatric cough (< 3-5 days to < 6 weeks), and chronic pediatric cough (> 2-8 weeks). Guidelines generally do not recommend over-the-counter or prescription cough medicines in acute pediatric cough, due to lack of evidence. In the expert survey, participants had differing opinions on which medicines were most suitable for treating acute pediatric cough, and noted that effective treatments are lacking for cough-related pain and sleep disruption. Overall, guidelines and experts agreed that chronic pediatric cough requires diagnostic investigations to identify the underlying cough-causing disease and thereby to guide treatment. There are unmet needs for new effective and safe treatments for acute pediatric cough, and for randomized controlled trials of existing treatments. Safety is a particular concern in this vulnerable patient population. There is also a need for better understanding of the causes, phenotypes, and prevalence of pediatric cough, and how this relates to its diagnosis and treatment. CONCLUSIONS: Whereas pediatric cough guidelines largely align with regard to the diagnosis and treatment of chronic cough, there is limited evidence-based guidance for the management of acute cough. There is a need for harmonization of pediatric cough management, and the development of standard guidelines suitable for all regions and patient circumstances.

Patient-reported outcome measures for life engagement in mental health: a systematic review.

BACKGROUND: Life engagement in the context of mental health is a broad term that describes positive health aspects relating to cognition, vitality, motivation and reward, and the ability to feel pleasure-concepts that are meaningful to patients. The aim of this systematic literature review was to identify validated patient-reported outcomes (PROs) that can assess any aspect of life engagement in adults, in the field of general mental health. METHODS: This was a systematic literature review of articles in English from the MEDLINE database (date of search: September 9, 2020). The search strategy had three components: (1) terms to capture PROs; (2) terms to capture mental health; and (3) terms to capture aspects of life engagement. Articles were eligible if they included a PRO that: (1) is named; (2) can be used across mental health disorders; (3) is used to assess any aspect of life engagement; and (4) has undergone psychometric validation and/or qualitative content validation. A list of PROs was extracted. RESULTS: A total of 1585 records were screened and 233 articles were eligible for inclusion. Within these 233 articles, 49 distinct PROs were identified, two of which specifically captured their authors' interpretation of life engagement: the Engaged Living Scale (ELS) and the Life Engagement Test (LET). However, while the ELS and LET covered motivation and reward, life fulfillment, and value-based living, neither scale captured the cognitive or vitality aspects of life engagement. The remaining identified PROs generally captured single aspects of life engagement, most commonly motivation/reward/energy-apathy, pleasure-anhedonia, and mental/psychological well-being. CONCLUSION: Numerous PROs are available that may capture aspects of life engagement. However, a need remains for a new PRO that can be used in clinical trials to provide a more comprehensive description of the improvements in life engagement that patients with mental health disorders may experience with successful treatment.

Functioning outcomes with adjunctive treatments for major depressive disorder: a systematic review of randomized placebo-controlled studies.

OBJECTIVE: Patients with major depressive disorder (MDD) with inadequate response to antidepressant treatment (ADT) may suffer a prolonged loss of functioning. This review aimed to determine if self-rated functional measures are informative in randomized placebo-controlled studies of adjunctive therapy in patients with MDD and inadequate response to ADT. METHODS: This was a systematic literature review of articles in any language from the MEDLINE database published between January 1990 and March 2017. Eligible studies met the following criteria: patients with MDD; inadequate response to at least one ADT; adjunctive therapy (pharmacological or otherwise) to ADT; placebo control group; randomized controlled trial or a post hoc analysis of a randomized controlled trial; reported a self-rated functioning scale. Study characteristics and functioning efficacy data were extracted. RESULTS: A total of 2,090 discrete records were screened, 293 full-text articles were assessed for eligibility, and 26 studies were included. All studies were acute (6-12 weeks) except for one 52-week study. The only self-rated functioning scale used in the included studies was the Sheehan Disability Scale (SDS). Of the 13 adjunctive agents identified, aripiprazole, brexpiprazole, edivoxetine, and risperidone improved functioning versus placebo (p<0.05), as measured by the SDS total or mean score. On the SDS "work/studies" item, only aripiprazole had a statistically significant benefit, in one study out of four. Thus, where a benefit was observed on the SDS total or mean, this was generally driven by improvement on the "social life" and "family life" items. A limitation of the review is that it only considered published literature from one database. CONCLUSION: The SDS, a self-rated functional measure, is informative in acute randomized placebo-controlled studies of adjunctive therapy in patients with MDD and inadequate response to ADT. However, the item that measures work performance may be less relevant to this population than the items that measure social and family life.

A regenerative microchannel neural interface for recording from and stimulating peripheral axons in vivo.

Neural interfaces are implanted devices that couple the nervous system to electronic circuitry. They are intended for long term use to control assistive technologies such as muscle stimulators or prosthetics that compensate for loss of function due to injury. Here we present a novel design of interface for peripheral nerves. Recording from axons is complicated by the small size of extracellular potentials and the concentration of current flow at nodes of Ranvier. Confining axons to microchannels of ~100 µm diameter produces amplified potentials that are independent of node position. After implantation of microchannel arrays into rat sciatic nerve, axons regenerated through the channels forming 'mini-fascicles', each typically containing ~100 myelinated fibres and one or more blood vessels. Regenerated motor axons reconnected to distal muscles, as demonstrated by the recovery of an electromyogram and partial prevention of muscle atrophy. Efferent motor potentials and afferent signals evoked by muscle stretch or cutaneous stimulation were easily recorded from the mini-fascicles and were in the range of 35-170 µV. Individual motor units in distal musculature were activated from channels using stimulus currents in the microampere range. Microchannel interfaces are a potential solution for applications such as prosthetic limb control or enhancing recovery after nerve injury.