Improving care for patients with multiple long-term conditions admitted to hospital: challenges and potential solutions.

Increasing numbers of people live with multiple long-term conditions. These people are more likely to be admitted to hospital, experience adverse outcomes and receive poorer quality care than those with a single condition. Hospitals remain organised around a model of single-organ, disease-specific care which is not equipped to meet the needs of people living with multiple long-term conditions. This article considers these challenges and explores potential solutions. These include different service models to provide holistic, multidisciplinary inpatient and outpatient care across specialty boundaries, training a workforce to deliver high-quality hospital care for people living with multiple long-term conditions, and developing technological, financial and cultural enablers of change. Considerably more research is required to fully appreciate the shared risk factors, underlying mechanisms, patterns and consequences of multiple long-term conditions. This is essential to design and deliver better structures and processes of hospital care for people living with multiple long-term conditions.

A study protocol to investigate if acipimox improves muscle function and sarcopenia: an open-label, uncontrolled, before-and-after experimental medicine feasibility study in community-dwelling older adults.

INTRODUCTION: Sarcopenia is the age-associated loss of muscle mass and strength. Nicotinamide adenine dinucleotide (NAD) plays a central role in both mitochondrial function and cellular ageing processes implicated in sarcopenia. NAD concentrations are low in older people with sarcopenia, and increasing skeletal muscle NAD concentrations may offer a novel therapy for this condition. Acipimox is a licensed lipid-lowering agent known to act as an NAD precursor. This open-label, uncontrolled, before-and-after proof-of-concept experimental medicine study will test whether daily supplementation with acipimox improves skeletal muscle NAD concentrations. METHODS AND ANALYSIS: Sixteen participants aged 65 and over with probable sarcopenia will receive acipimox 250 mg and aspirin 75 mg orally daily for 4 weeks, with the frequency of acipimox administration being dependent on renal function. Muscle biopsy of the vastus lateralis and MRI scanning of the lower leg will be performed at baseline before starting acipimox and after 3 weeks of treatment. Adverse events will be recorded for the duration of the trial. The primary outcome, analysed in a per-protocol population, is the change in skeletal muscle NAD concentration between baseline and follow-up. Secondary outcomes include changes in phosphocreatine recovery rate by 31P magnetic resonance spectroscopy, changes in physical performance and daily activity (handgrip strength, 4 m walk and 7-day accelerometry), changes in skeletal muscle mitochondrial respiratory function, changes in skeletal muscle mitochondrial DNA copy number and changes in NAD concentrations in whole blood as a putative biomarker for future participant selection. ETHICS AND DISSEMINATION: The trial is approved by the UK Medicines and Healthcare Products Regulatory Agency (EuDRACT 2021-000993-28) and UK Health Research Authority and Northeast - Tyne and Wear South Research Ethics Committee (IRAS 293565). Results will be made available to participants, their families, patients with sarcopenia, the public, regional and national clinical teams, and the international scientific community. PROTOCOL: Acipimox feasibility study Clinical Trial Protocol V.2 2/11/21. TRIAL REGISTRATION NUMBER: The ISRCTN trial database (ISRCTN87404878).

Visual Exploration While Walking With and Without Visual Cues in Parkinson's Disease: Freezer Versus Non-Freezer.

BACKGROUND: Visual cues can improve gait in Parkinson's disease (PD), including those experiencing freezing of gait (FOG). However, responses are variable and underpinning mechanisms remain unclear. Visuo-cognitive processing (measured through visual exploration) has been implicated in cue response, but this has not been comprehensively examined. OBJECTIVE: To examine visual exploration and gait with and without visual cues in PD who do and do not self-report FOG, and healthy controls (HC). METHODS: 17 HC, 21 PD without FOG, and 22 PD with FOG walked with and without visual cues, under single and dual-task conditions. Visual exploration (ie, saccade frequency, duration, peak velocity, amplitude, and fixation duration) was measured via mobile eye-tracking and gait (ie, gait speed, stride length, foot strike angle, stride time, and stride time variability) with inertial sensors. RESULTS: PD had impaired gait compared to HC, and dual-tasking made gait variables worse across groups (all P < .01). Visual cues improved stride length, foot strike angle, and stride time in all groups (P < .01). Visual cueing also increased saccade frequency, but reduced saccade peak velocity and amplitude in all groups (P < .01). Gait improvement related to changes in visual exploration with visual cues in PD but not HC, with relationships dependent on group (FOG vs non-FOG) and task (single vs dual). CONCLUSION: Visual cues improved visual exploration and gait outcomes in HC and PD, with similar responses in freezers and non-freezers. Freezer and non-freezer specific associations between cue-related changes in visual exploration and gait indicate different underlying visuo-cognitive processing within these subgroups for cue response.

Ocular microtremor: a structured review.

Ocular microtremor (OMT) is the smallest of three involuntary fixational micro eye movements, which has led to it being under researched in comparison. The link between OMT and brain function generates a strong rationale for further study as there is potential for its use as a biomarker in populations with neurological injury and disease. This structured review focused on populations previously studied, instrumentation used for measurement, commonly reported OMT outcomes, and recommendations concerning protocol design and future studies. Current methods of quantifying OMT will be reviewed to analyze their efficacy and efficiency and guide potential development and understanding of novel techniques. Electronic databases were systematically searched and compared with predetermined inclusion criteria. 216 articles were identified in the search and screened by two reviewers. 16 articles were included for review. Findings showed that piezoelectric probe is the most common method of measuring OMT, with fewer studies involving non-invasive approaches, such as contact lenses and laser imaging. OMT frequency was seen to be reduced during general anesthesia at loss of consciousness and in neurologically impaired participants when compared to healthy adults. We identified the need for a non-invasive technique for measuring OMT and highlight its potential in clinical applications as an objective biomarker for neurological assessments. We highlight the need for further research on the clinical validation of OMT to establish its potential to identify or predict a meaningful clinical or functional state, specifically, regarding accuracy, precision, and reliability of OMT.

Combination of Clinical and Gait Measures to Classify Fallers and Non-Fallers in Parkinson's Disease.

Although the multifactorial nature of falls in Parkinson's disease (PD) is well described, optimal assessment for the identification of fallers remains unclear. Thus, we aimed to identify clinical and objective gait measures that best discriminate fallers from non-fallers in PD, with suggestions of optimal cutoff scores. METHODS: Individuals with mild-to-moderate PD were classified as fallers (n = 31) or non-fallers (n = 96) based on the previous 12 months' falls. Clinical measures (demographic, motor, cognitive and patient-reported outcomes) were assessed with standard scales/tests, and gait parameters were derived from wearable inertial sensors (Mobility Lab v2); participants walked overground, at a self-selected speed, for 2 min under single and dual-task walking conditions (maximum forward digit span). Receiver operating characteristic curve analysis identified measures (separately and in combination) that best discriminate fallers from non-fallers; we calculated the area under the curve (AUC) and identified optimal cutoff scores (i.e., point closest-to-(0,1) corner). RESULTS: Single gait and clinical measures that best classified fallers were foot strike angle (AUC = 0.728; cutoff = 14.07°) and the Falls Efficacy Scale International (FES-I; AUC = 0.716, cutoff = 25.5), respectively. Combinations of clinical + gait measures had higher AUCs than combinations of clinical-only or gait-only measures. The best performing combination included the FES-I score, New Freezing of Gait Questionnaire score, foot strike angle and trunk transverse range of motion (AUC = 0.85). CONCLUSION: Multiple clinical and gait aspects must be considered for the classification of fallers and non-fallers in PD.

Exploring the feasibility of technological visuo-cognitive training in Parkinson's: Study protocol for a pilot randomised controlled trial.

Visual and cognitive dysfunction are common in Parkinson's disease and relate to balance and gait impairment, as well as increased falls risk and reduced quality of life. Vision and cognition are interrelated (termed visuo-cognition) which makes intervention complex in people with Parkinson's (PwP). Non-pharmacological interventions for visuo-cognitive deficits are possible with modern technology, such as combined mobile applications and stroboscopic glasses, but evidence for their effectiveness in PwP is lacking. We aim to investigate whether technological visuo-cognitive training (TVT) can improve visuo-cognitive function in PwP. We will use a parallel group randomised controlled trial to evaluate the feasibility and acceptability of TVT versus standard care in PwP. Forty PwP who meet our inclusion criteria will be randomly assigned to one of two visuo-cognitive training interventions. Both interventions will be carried out by a qualified physiotherapist in participants own homes (1-hour sessions, twice a week, for 4 weeks). Outcome measures will be assessed on anti-parkinsonian medication at baseline and at the end of the 4-week intervention. Feasibility of the TVT intervention will be assessed in relation to safety and acceptability of the technological intervention, compliance and adherence to the intervention and usability of equipment in participants homes. Additionally, semi structured interviews will be conducted to explore participants' experience of the technology. Exploratory efficacy outcomes will include change in visual attention measured using the Trail Making Test as well as changes in balance, gait, quality of life, fear of falling and levels of activity. This pilot study will focus on the feasibility and acceptability of TVT in PwP and provide preliminary data to support the design of a larger, multi-centre randomised controlled trial. This trial is registered at isrctn.com (ISRCTN46164906).

Visual Cues for Turning in Parkinson's Disease.

Turning is a common impairment of mobility in people with Parkinson's disease (PD), which increases freezing of gait (FoG) episodes and has implications for falls risk. Visual cues have been shown to improve general gait characteristics in PD. However, the effects of visual cues on turning deficits in PD remains unclear. We aimed to (i) compare the response of turning performance while walking (180° and 360° turns) to visual cues in people with PD with and without FoG; and (ii) examine the relationship between FoG severity and response to visual cues during turning. This exploratory interventional study measured turning while walking in 43 participants with PD (22 with self-reported FoG) and 20 controls using an inertial sensor placed at the fifth lumbar vertebrae region. Participants walked straight and performed 180° and 360° turns midway through a 10 m walk, which was done with and without visual cues (starred pattern). The turn duration and velocity response to visual cues were assessed using linear mixed effects models. People with FoG turned slower and longer than people with PD without FoG and controls (group effect: p < 0.001). Visual cues reduced the velocity of turning 180° across all groups and reduced the velocity of turning 360° in people with PD without FoG and controls. FoG severity was not significantly associated with response to visual cues during turning. Findings suggest that visual cueing can modify turning during walking in PD, with response influenced by FoG status and turn amplitude. Slower turning in response to visual cueing may indicate a more cautious and/or attention-driven turning pattern. This study contributes to our understanding of the influence that cues can have on turning performance in PD, particularly in freezers, and will aid in their therapeutic application.

MET-PREVENT: metformin to improve physical performance in older people with sarcopenia and physical prefrailty/frailty - protocol for a double-blind, randomised controlled proof-of-concept trial.

INTRODUCTION: Skeletal muscle dysfunction is central to both sarcopenia and physical frailty, which are associated with a wide range of adverse outcomes including falls and fractures, longer hospital stays, dependency and the need for care. Resistance training may prevent and treat sarcopenia and physical frailty, but not everyone can or wants to exercise. Finding alternatives is critical to alleviate the burden of adverse outcomes associated with sarcopenia and physical frailty. This trial will provide proof-of-concept evidence as to whether metformin can improve physical performance in older people with sarcopenia and physical prefrailty or frailty. METHODS AND ANALYSIS: MET-PREVENT is a parallel group, double-blind, placebo-controlled proof-of-concept trial. Trial participants can participate from their own homes, including completing informed consent and screening assessments. Eligible participants with low grip strength or prolonged sit-to-stand time together with slow walk speed will be randomised to either oral metformin hydrochloride 500 mg tablets or matched placebo, taken three times a day for 4 months. The recruitment target is 80 participants from two secondary care hospitals in Newcastle and Gateshead, UK. Local primary care practices will act as participant identification centres. Randomisation will be performed using a web-based minimisation system with a random element, balancing on sex and baseline walk speed. Participants will be followed up for 4 months post-randomisation, with outcomes collected at baseline and 4 months. The primary outcome measure is the four metre walk speed at the 4-month follow-up visit. ETHICS AND DISSEMINATION: The trial has been approved by the Liverpool NHS Research Ethics Committee (20/NW/0470), the Medicines and Healthcare Regulatory Authority (EudraCT 2020-004023-16) and the UK Health Research Authority (IRAS 275219). Results will be made available to participants, their families, patients with sarcopenia, the public, regional and national clinical teams, and the international scientific community. TRIAL REGISTRATION NUMBER: ISRCTN29932357.

Performance of the SarQoL quality of life tool in a UK population of older people with probable sarcopenia and implications for use in clinical trials: findings from the SarcNet registry.

BACKGROUND: The Sarcopenia Quality of Life (SarQoL) questionnaire is a disease-specific sarcopenia quality of life tool. We aimed to independently assess SarQoL with a particular focus on its suitability as a clinical trial outcome measure. METHODS: We analysed data from the UK Sarcopenia Network and Registry. Measures of physical performance and lean mass were collected at baseline. SarQoL and the Strength, Assistance, Rise, Climb - Falls (SARC-F) questionnaire (to assess functional ability) were collected at both baseline and six-month follow-up. Global changes in fitness and quality of life at 6 months were elicited on seven-point Likert scales. Internal consistency was assessed using Cronbach's alpha. Responsiveness (Cohen's d and Guyatt coefficients) and minimum clinically important differences were calculated for participants reporting slight improvement or worsening in their global scores. Concurrent validity was assessed by correlating baseline SarQoL scores with measures of physical performance and functional ability. RESULTS: We analysed data from 147 participants, 125 of whom underwent follow up assessment; mean age 78 years; 72 (49%) were women. Internal consistency was good; Cronbach's alpha was 0.944 at baseline and 0.732 at telephone follow-up. Correlation between baseline and follow-up SarQoL was weak (r = 0.27; p = 0.03). The minimum clinically important improvement ranged from 5 to 21 points giving trial sample size estimates of 25-100 participants. SarQoL scores were moderately correlated with handgrip (r = 0.37; p < 0.001), SARC-F (r = - 0.45; p < 0.001), short physical performance battery (r = 0.48; p < 0.001) and 4-m walk speed (r = 0.48; p < 0.001). CONCLUSIONS: SarQoL has acceptable performance in older UK participants with probable sarcopenia and is sufficiently responsive for use in clinical trials for sarcopenia.

Developing a UK sarcopenia registry: recruitment and baseline characteristics of the SarcNet pilot.

BACKGROUND: sarcopenia registries are a potential method to meet the challenge of recruitment to sarcopenia trials. We tested the feasibility of setting up a UK sarcopenia registry, the feasibility of recruitment methods and sought to characterise the pilot registry population. METHODS: six diverse UK sites took part, with potential participants aged 65 and over approached via mailshots from local primary care practices. Telephone pre-screening using the SARC-F score was followed by in-person screening and baseline visit. Co-morbidities, medications, grip strength, Short Physical Performance Battery, bioimpedance analysis, Geriatric Depression Score, Montreal Cognitive Assessment, Sarcopenia Quality of Life score were performed and permission sought for future recontact. Descriptive statistics for recruitment rates and baseline measures were generated; an embedded randomised trial examined the effect of a University logo on the primary care mailshot on recruitment rates. RESULTS: sixteen practices contributed a total of 3,508 letters. In total, 428 replies were received (12% response rate); 380 underwent telephone pre-screening of whom 215 (57%) were eligible to attend a screening visit; 150 participants were recruited (40% of those pre-screened) with 147 contributing baseline data. No significant difference was seen in response rates between mailshots with and without the logo (between-group difference 1.1% [95% confidence interval -1.0% to 3.4%], P = 0.31). The mean age of enrollees was 78 years; 72 (49%) were women. In total, 138/147 (94%) had probable sarcopenia on European Working Group on Sarcopenia 2019 criteria and 145/147 (98%) agreed to be recontacted about future studies. CONCLUSION: recruitment to a multisite UK sarcopenia registry is feasible, with high levels of consent for recontact.

Bladder training for urinary tract symptoms in Parkinson disease: A randomized controlled trial.

OBJECTIVE: To assess the feasibility and efficacy of bladder training for troublesome lower urinary tract symptoms (LUTS) in Parkinson disease (PD). METHODS: In this single-center, single-blinded, randomized controlled trial, participants with a history of PD and LUTS were randomized to a 12-week bladder training program (BT) or conservative advice (CA). Outcome measures included a 3-day volume frequency diary, International Consultation on Incontinence Questionnaire (ICIQ)-Overactive Bladder Module, and ICIQ-Quality of Life Module. Co-primary endpoints were (1) patient perception of change and (2) change in number of urgency episodes at 12 weeks. Secondary endpoints included change in ICIQ scores, number of micturitions, and volume voided. RESULTS: Thirty-eight participants were randomized (18 to CA, 20 to BT). Both CA and BT were associated with significant improvements in volume voided, number of micturitions, symptom severity scores, and measures of quality of life (all p < 0.05). At 12 weeks, compared to CA, BT was associated with significant superiority on patient perception of improvement (p = 0.001), significantly greater reductions in number of voids in 24 hours (mean decrease 2.3 ± 0.8 voids vs 0.3 ± 0.5 [p < 0.05]), and greater reductions in interference with daily life (2.1 ± 0.8 point improvement vs 0.3 ± 0.7 point deterioration [p < 0.05]). BT was not associated with change in urgency episodes (mean change 2.4 ± 1.5 urgency episodes vs 3.5 ± 1.5 [p NS]). At 20 weeks, BT remained associated with greater improvement in interference in daily life. Loss of significance in other measures may reflect loss of power from loss to follow-up. CONCLUSION: This controlled trial demonstrated the potential benefits of BT for LUTS in PD. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with PD and LUTS, BT significantly increased patient perception of improvement but did not significantly reduce urgency episodes.

Analysis of Dextromethorphan and Three Metabolites in Decomposed Skeletal Tissues by UPLC-QToF-MS: Comparison of Acute and Repeated Drug Exposures.

Ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QToF-MS) analysis of dextromethorphan (DXM) and its metabolites-dextrorphan, 3-methoxymorphinan (3-MEM) and 3-hydroxymorphinan-in skeletal remains of rats exposed to DXM under different dosing patterns is described. Rats (n = 20) received DXM in one of four dosing patterns: acute (ACU1 or ACU2-100 or 200 mg/kg, i.p.; n = 5, respectively) or repeated (REP1 or REP2-3 doses of 25 or 50 mg/kg, i.p., 30 min apart; n = 5, respectively). Drug-free animals (n = 5) served as negative controls. Following euthanasia, the animals decomposed to skeleton outdoors. Bones were sorted by animal and skeletal element (vertebra, femur, pelvis, tibia, rib and skull), washed, air-dried and pulverized prior to dynamic methanolic drug extraction, filtration/pass-through extraction and analysis by UPLC-QToF-MS in positive electrospray ionization mode. Analyte levels (expressed as mass-normalized response ratios, RR/m) differed significantly between ACU1 and ACU2 (Mann-Whitney (MW), P < 0.05) in all skeletal elements for all analytes investigated, and between REP1 and REP2 in most skeletal elements for 3-MEM and 3-HOM, but in all skeletal elements for DXM. Between ACU1 and ACU2, and between REP1 and REP2, analyte level ratios (RRi/RRj) differed significantly (MW, P < 0.05) in 3/6 to 6/6 skeletal elements, depending on the ratios concerned, with no analyte level ratio differing significantly between both ACU1 vs ACU2 and REP1 vs REP2. Kruskal-Wallis (KW) analysis showed skeletal element to be a main effect for all analyte levels and analyte level ratios in all ACU and REP groups examined (P < 0.05). For data pooled only according to exposure pattern, KW analysis showed dose pattern to be a main effect for both analyte levels and analyte level ratios (P < 0.05). These data illustrate a dependence of these measures on dose, dose pattern and skeletal element, suggesting that some exposure patterns may be distinguished by toxicological analysis of bone.

Defining delirium in idiopathic Parkinson's disease: A systematic review.

BACKGROUND: Parkinson's disease patients may be at increased risk of delirium and developing adverse outcomes, such as cognitive decline and increased mortality. Delirium is an acute state of confusion that has overlapping symptoms with Parkinson's dementia, making it difficult to identify. This study aimed to determine the diagnostic criteria, prevalence, management strategies and outcomes of delirium in Parkinson's through a systematic review of the literature. METHODS: Seven databases were used to identify all articles published before February 2017 comprising two key terms: "Parkinson's Disease" and "delirium". Data were extracted from studies meeting predefined inclusion criteria. RESULTS: Twenty articles were identified. Delirium prevalence in Parkinson's ranged from 0.3 to 60% depending on setting; a diagnosis of Parkinson's was associated with an increased risk of developing delirium. Delirium was identified/diagnosed using seven different criteria. Delirium may be associated with an increased length of hospital stay and worsening motor symptoms. We did not identify any studies examining the management of delirium in Parkinson's. DISCUSSION: This review highlights the paucity of well-designed, appropriately powered studies investigating delirium in Parkinson's. The results suggest that delirium is a significant issue in people with Parkinson's and that having delirium may be a risk factor for adverse outcomes, particularly in inpatient settings. Further prospective research is needed to accurately determine the prevalence of delirium in Parkinson's, its management strategies and outcomes, and to evaluate diagnostic criteria to differentiate between the overlapping symptoms of Parkinson's and delirium.

The Pattern of Hospital Admissions Prior to Care Home Placement in People With Parkinson's Disease: Evidence of a Period of Crisis for Patients and Carers.

Objectives: We hypothesized that the number and length of hospital admissions in people with Parkinson's disease (PD) would increase immediately prior to admission to a care home relative to those who were able to continue living at home or who died. Method: PD patients at Hoehn and Yahr Stages III to V were followed-up over two and a half years with deaths and care home placements recorded. Hospital admissions data were collected over this period. Results: Of 286 patients included in the study, 7.3% entered a care home and 28.3% died. In the final 120 days prior to the study exit point (care home placement, death, or continued living at home), longer hospital stay was significantly associated with care home placement, after adjusting for the competing risk of death. Conclusion: Our data provide evidence that, for many people with PD, a period of crisis is reached immediately prior to care home placement.

200 Years of Parkinson's disease: what have we learnt from James Parkinson?

2017 marks 200 years since James Parkinson's published his 'Essay on the Shaking Palsy'. Although now most famous for describing the condition that came to bear his name, Parkinson had a wide range of interests and his influence spread beyond medicine. In this review, we provide a biography of James Parkinson's remarkable life.Parkinson's paper not only comprehensively described the symptoms of Parkinson's disease (PD), but challenged his peers to better understand the pathophysiology of the PD. Key observation over the next 2 centuries, included the recognition of the link between the substantia nigra and PD and the discoveries of dopamine deficiency in patients with PD. We review the subsequent development of pharmacological and surgical therapies. Despite great progress over the last 200 years, Parkinson's hopes for a 'cure if employed early enough' or that 'some remedial process may ere long be discovered by which at least the progression of the disease may be stopped' remain apposite today and we reflect on the challenges ahead for the next century.

Using chemical and DNA marker analysis to authenticate a high-value food, manuka honey.

Ensuring the authenticity of food is a rapidly emerging issue, especially in regard to high-value products that are marketed through increasingly complex global food chains. With the ever-increasing potential for mislabeling, fraud and adulteration, governments are increasingly having to invest in, and assure, the authenticity of foods in international trade. This is particularly the case for manuka honey, an iconic New Zealand food product. We show how the authenticity of a specific type of honey can be determined using a combination of chemicals derived from nectar and DNA derived from pollen. We employ an inter-disciplinary approach to evaluate a selection of authenticity markers, followed by classification modelling to produce criteria that consistently identify manuka honey from New Zealand. The outcome of our work provides robust identification criteria that can be applied in a regulatory setting to authenticate a high-value natural food. Our approach can transfer to other foods where assurance of authenticity must take into account a high level of natural variability.

Poor Sleep Quality and Progression of Gait Impairment in an Incident Parkinson's Disease Cohort.

Abnormal sleep may associate with cognitive decline in Parkinson's disease (PD). Furthermore, sleep dysfunction may associate with worse motor outcome. We hypothesised that PD patients with poor quality sleep would have greater progression in gait dysfunction, due to structural and functional overlap in networks subserving sleep and gait regulation. 12 PD patients and 12 age-matched controls completed longitudinal follow-up over 36 months. Poor sleep efficiency and greater sleep fragmentation correlated significantly with progression of step-width variability, a gait characteristic mediated by postural control, providing evidence that poor sleep in PD is associated with a more rapid deterioration in gait.

Herbivore regulation of plant abundance in aquatic ecosystems.

Herbivory is a fundamental process that controls primary producer abundance and regulates energy and nutrient flows to higher trophic levels. Despite the recent proliferation of small-scale studies on herbivore effects on aquatic plants, there remains limited understanding of the factors that control consumer regulation of vascular plants in aquatic ecosystems. Our current knowledge of the regulation of primary producers has hindered efforts to understand the structure and functioning of aquatic ecosystems, and to manage such ecosystems effectively. We conducted a global meta-analysis of the outcomes of plant-herbivore interactions using a data set comprised of 326 values from 163 studies, in order to test two mechanistic hypotheses: first, that greater negative changes in plant abundance would be associated with higher herbivore biomass densities; second, that the magnitude of changes in plant abundance would vary with herbivore taxonomic identity. We found evidence that plant abundance declined with increased herbivore density, with plants eliminated at high densities. Significant between-taxa differences in impact were detected, with insects associated with smaller reductions in plant abundance than all other taxa. Similarly, birds caused smaller reductions in plant abundance than echinoderms, fish, or molluscs. Furthermore, larger reductions in plant abundance were detected for fish relative to crustaceans. We found a positive relationship between herbivore species richness and change in plant abundance, with the strongest reductions in plant abundance reported for low herbivore species richness, suggesting that greater herbivore diversity may protect against large reductions in plant abundance. Finally, we found that herbivore-plant nativeness was a key factor affecting the magnitude of herbivore impacts on plant abundance across a wide range of species assemblages. Assemblages comprised of invasive herbivores and native plant assemblages were associated with greater reductions in plant abundance compared with invasive herbivores and invasive plants, native herbivores and invasive plants, native herbivores and mixed-nativeness plants, and native herbivores and native plants. By contrast, assemblages comprised of native herbivores and invasive plants were associated with lower reductions in plant abundance compared with both mixed-nativeness herbivores and native plants, and native herbivores and native plants. However, the effects of herbivore-plant nativeness on changes in plant abundance were reduced at high herbivore densities. Our mean reductions in aquatic plant abundance are greater than those reported in the literature for terrestrial plants, but lower than aquatic algae. Our findings highlight the need for a substantial shift in how biologists incorporate plant-herbivore interactions into theories of aquatic ecosystem structure and functioning. Currently, the failure to incorporate top-down effects continues to hinder our capacity to understand and manage the ecological dynamics of habitats that contain aquatic plants.