Synthesis of ionizable lipopolymers using split-Ugi reaction for pulmonary delivery of various size RNAs and gene editing.

We present an efficient approach for synthesizing cationic poly(ethylene imine) derivatives using the multicomponent split-Ugi reaction to rapidly create a library of complex functional ionizable lipopolymers. We synthesized a diverse library of 155 polymers, formulated them into polyplexes to establish structure-activity relationships crucial for endosomal escape and efficient transfection. After discovering a lead structure, lipopolymer-lipid hybrid nanoparticles are introduced to preferentially deliver to and elicit effective mRNA transfection in lung endothelium and immune cells, including T cells with low in vivo toxicity. The lipopolymer-lipid hybrid nanoparticles showed 300-fold improvement in systemic mRNA delivery to the lung compared to in vivo -JetPEI ® . Lipopolymer-lipid hybrid nanoparticles demonstrated efficient delivery of mRNA-based therapeutics for treatment of two different disease models. Lewis Lung cancer progression was significantly delayed after treatment with loaded IL-12 mRNA in U155@lipids after repeated i.v. administration. Systemic delivery of human CFTR (hCFTR) mRNA resulted in production of functional form of CFTR protein in the lungs. The functionality of hCFTR protein was confirmed by restoration of CFTR- mediated chloride secretion in conductive airway epithelia in CFTR knockout mice after nasal instillation of hCFTR mRNA loaded U155@lipids. We further showed that, U155@lipids nanoparticles can deliver complex CRISPR-Cas9 based RNA cargo to the lung, achieving 5.6 ± 2.4 % gene editing in lung tissue. Moreover, we demonstrated successful PD-1 gene knockout of T cells in vivo . Our results highlight a versatile delivery platform for systemic delivering of mRNA of various sizes for gene therapy for a variety of therapeutics.

A cytomics-on-a-chip platform and diagnostic model stratifies risk for oral lichenoid conditions.

OBJECTIVE: A small fraction of oral lichenoid conditions (OLC) have potential for malignant transformation. Distinguishing OLCs from other oral potentially malignant disorders (OPMDs) can help prevent unnecessary concern or testing, but accurate identification by nonexpert clinicians is challenging due to overlapping clinical features. In this study, the authors developed a 'cytomics-on-a-chip' tool and integrated predictive model for aiding the identification of OLCs. STUDY DESIGN: All study subjects underwent both scalpel biopsy for histopathology and brush cytology. A predictive model and OLC Index comprising clinical, demographic, and cytologic features was generated to discriminate between subjects with lichenoid (OLC+) (N = 94) and nonlichenoid (OLC-) (N = 237) histologic features in a population with OPMDs. RESULTS: The OLC Index discriminated OLC+ and OLC- subjects with area under the curve (AUC) of 0.76. Diagnostic accuracy of the OLC Index was not significantly different from expert clinician impressions, with AUC of 0.81 (P = .0704). Percent agreement was comparable across all raters, with 83.4% between expert clinicians and histopathology, 78.3% between OLC Index and expert clinician, and 77.3% between OLC Index and histopathology. CONCLUSIONS: The cytomics-on-a-chip tool and integrated diagnostic model have the potential to facilitate both the triage and diagnosis of patients presenting with OPMDs and OLCs.

A brief review of cytology in dentistry.

Oral cytology is a non-invasive adjunctive diagnostic tool with a number of potential applications in the practice of dentistry. This brief review begins with a history of cytology in medicine and how cytology was initially applied in oral medicine. A description of the different technical aspects of oral cytology is provided, including the collection and processing of oral cytological samples, and the microscopic interpretation and reporting, along with their advantages and limitations. Applications for oral cytology are listed with a focus on the triage of patients presenting with oral potentially malignant disorders and oral mucosal infections. Furthermore, the utility of oral cytology roles across both expert (for example, secondary oral medicine or tertiary head and neck oncology services) and non-expert (for example, primary care general dental practice) clinical settings is explored. A detailed section covers the evidence-base for oral cytology as a diagnostic adjunctive technique in both the early detection and monitoring of patients with oral cancer and oral epithelial dysplasia. The review concludes with an exploration of future directions, including the integration of artificial intelligence for automated analysis and point of care 'smart diagnostics', thereby offering some insight into future opportunities for a wider application of oral cytology in dentistry.

Intranasal SARS-CoV-2 RBD decorated nanoparticle vaccine enhances viral clearance in the Syrian hamster model.

Multiple vaccines have been developed and licensed for SARS-CoV-2. While these vaccines reduce disease severity, they do not prevent infection, and SARS-CoV-2 continues to spread and evolve. To prevent infection and limit transmission, vaccines must be developed that induce immunity in the respiratory tract. Therefore, we performed proof-of-principle vaccination studies with an intranasal nanoparticle vaccine against SARS-CoV-2. The vaccine candidate consisted of the self-assembling 60-subunit I3-01 protein scaffold covalently decorated with the SARS-CoV-2 receptor binding domain (RBD) using the SpyCatcher-SpyTag system. We verified the intended antigen display features by reconstructing the I3-01 scaffold to 3.4A using cryo-EM, and then demonstrated that the scaffold was highly saturated when grafted with RBD. Using this RBD-grafted SpyCage scaffold (RBD+SpyCage), we performed two unadjuvanted intranasal vaccination studies in the "gold-standard" preclinical Syrian hamster model. Hamsters received two vaccinations 28 days apart, and were then challenged 28 days post-boost with SARS-CoV-2. The initial study focused on assessing the immunogenicity of RBD+SpyCage, which indicated that vaccination of hamsters induced a non-neutralizing antibody response that enhanced viral clearance but did not prevent infection. In an expanded study, we demonstrated that covalent bonding of RBD to the scaffold was required to induce an antibody response. Consistent with the initial study, animals vaccinated with RBD+SpyCage more rapidly cleared SARS-CoV-2 from both the upper and lower respiratory tract. These findings demonstrate the intranasal SpyCage vaccine platform can induce protection against SARS-CoV-2 and, with additional modifications to improve immunogenicity, is a versatile platform for the development of intranasal vaccines targeting respiratory pathogens.

Estimating the economic impact of acute coronary syndrome in New Zealand over time (ANZACS-QI 64): a national registry-based cost burden study.

OBJECTIVES: To estimate the changes in costs associated with acute coronary syndrome (ACS) admissions in New Zealand (NZ) public hospitals over a 12-year period. DESIGN: A cost-burden study of ACS in NZ was conducted from the NZ healthcare system perspective. SETTING: Hospital admission costs were estimated using relevant diagnosis-related groups and their costs for publicly funded casemix hospitalisations, and applied to 190 364 patients with ACS admitted to NZ public hospitals between 2007 and 2018 identified from routine national hospital datasets. Trends in the costs of index ACS hospitalisation, hospital admissions costs, coronary revascularisation and all-cause mortality up to 1 year were evaluated. All costs were presented as 2019 NZ dollars. PRIMARY OUTCOME MEASURES: Healthcare costs attributed to ACS admissions in NZ over time. RESULTS: Between 2007 and 2018, there was a 42% decrease in costs attributed to ACS (NZ$7.7 million (M) to NZ$4.4 M per 100 000 per year), representing a decrease of NZ$298 827 per 100 000 population per year. Mean admission costs associated with each admission declined from NZ$18 411 in 2007 to NZ$16 898 over this period (p<0.001) after adjustment for key clinical and procedural characteristics. These reductions were against a background of increased use of coronary revascularisation (23.1% (2007) to 38.1% (2018)), declining ACS admissions (366-252 per 100 000 population) and an improvement in 1-year survival post-ACS. Nevertheless, the total ACS cost burden remained considerable at NZ$237 M in 2018. CONCLUSIONS: The economic cost of hospitalisations for ACS in NZ decreased considerably over time. Further studies are warranted to explore the association between reductions in ACS cost burden and changes in the management of ACS.

Oral Cancer Screening: Past, Present, and Future.

Oral cancer is a major public health problem, and there is an increasing trend for oral cancer to affect young men and women. Public awareness is poor, and many patients present with late-stage disease, contributing to high mortality. Oral cancer is often preceded by a clinical premalignant phase accessible to visual inspection, and thus there are opportunities for earlier detection and to reduce morbidity and mortality. Screening asymptomatic individuals by systematic visual oral examinations to detect the disease has been shown to be feasible. A positive screen includes both oral cancer and oral potentially malignant disorders. We review key screening studies undertaken, including 1 randomized clinical trial. Screening of high-risk groups is cost-effective. Strengths and weaknesses of oral cancer screening studies are presented to help guide new research in primary care settings and invigorated by the prospect of using emerging new technologies that may help to improve discriminatory accuracy of case detection. Most national organizations, including the US Preventive Services Task Force, have so far not recommended population-based screening due a lack of sufficient evidence that screening leads to a reduction in oral cancer mortality. Where health care resources are high, opportunistic screening in dental practices is recommended, although the paucity of research in primary care is alarming. The results of surveys suggest that dentists do perform oral cancer screenings, but there is only weak evidence that screening in dental practices leads to downstaging of disease. Where health care resources are low, the feasibility of using primary health care workers for oral cancer screening has been tested, and measures indicate good outcomes. Most studies reported in the literature are based on 1 round of screening, whereas screening should be a continuous process. This review identifies a huge potential for new research directions on screening for oral cancer.

Nuclear F-actin Cytology in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma.

Oral cavity cancer has a low 5-y survival rate, but outcomes improve when the disease is detected early. Cytology is a less invasive method to assess oral potentially malignant disorders relative to the gold-standard scalpel biopsy and histopathology. In this report, we aimed to determine the utility of cytological signatures, including nuclear F-actin cell phenotypes, for classifying the entire spectrum of oral epithelial dysplasia and oral squamous cell carcinoma. We enrolled subjects with oral potentially malignant disorders, subjects with previously diagnosed malignant lesions, and healthy volunteers without lesions and obtained brush cytology specimens and matched scalpel biopsies from 486 subjects. Histopathological assessment of the scalpel biopsy specimens classified lesions into 6 categories. Brush cytology specimens were analyzed by machine learning classifiers trained to identify relevant cytological features. Multimodal diagnostic models were developed using cytology results, lesion characteristics, and risk factors. Squamous cells with nuclear F-actin staining were associated with early disease (i.e., lower proportions in benign lesions than in more severe lesions), whereas small round parabasal-like cells and leukocytes were associated with late disease (i.e., higher proportions in severe dysplasia and carcinoma than in less severe lesions). Lesions with the impression of oral lichen planus were unlikely to be either dysplastic or malignant. Cytological features substantially improved upon lesion appearance and risk factors in predicting squamous cell carcinoma. Diagnostic models accurately discriminated early and late disease with AUCs (95% CI) of 0.82 (0.77 to 0.87) and 0.93 (0.88 to 0.97), respectively. The cytological features identified here have the potential to improve screening and surveillance of the entire spectrum of oral potentially malignant disorders in multiple care settings.

Oncogenes overexpressed in metastatic oral cancers from patients with pain: potential pain mediators released in exosomes.

Oral cancer patients experience pain at the site of the primary cancer. Patients with metastatic oral cancers report greater pain. Lack of pain identifies patients at low risk of metastasis with sensitivity = 0.94 and negative predictive value = 0.89. In the same cohort, sensitivity and negative predictive value of depth of invasion, currently the best predictor, were 0.95 and 0.92, respectively. Cancer pain is attributed to cancer-derived mediators that sensitize neurons and is associated with increased neuronal density. We hypothesized that pain mediators would be overexpressed in metastatic cancers from patients reporting high pain. We identified 40 genes overexpressed in metastatic cancers from patients reporting high pain (n = 5) compared to N0 cancers (n = 10) and normal tissue (n = 5). The genes are enriched for functions in extracellular matrix organization and angiogenesis. They have oncogenic and neuronal functions and are reported in exosomes. Hierarchical clustering according to expression of neurotrophic and axon guidance genes also separated cancers according to pain and nodal status. Depletion of exosomes from cancer cell line supernatant reduced nociceptive behavior in a paw withdrawal assay, supporting a role for exosomes in cancer pain. The identified genes and exosomes are potential therapeutic targets for stopping cancer and attenuating pain.

Long-term changes in adipose tissue gene expression following bariatric surgery.

OBJECTIVE: Patients undergoing bariatric surgery present long-term metabolic improvements and reduced type 2 diabetes risk, despite long-term weight regain. We hypothesized that part of these protective effects could be linked to altered gene expression in white adipose tissue (WAT). METHODS: Transcriptomic profiling by gene microarray was performed in abdominal subcutaneous WAT from women before (n = 50) and two (n = 49) and five (n = 38) years after Roux-en-Y gastric bypass (RYGB) surgery as well as in 28 age-matched nonoperated women. RESULTS: In the obese women, the average body weight decrease was 38 kg 2 years postsurgery followed by an 8 kg weight regain between 2 and 5 years. Most of the long-term changes in WAT gene expression occurred during the first 2 years. However, a subset of genes encoding proteins involved in inflammation displayed a continued decrease between baseline, 2 and 5 years, respectively; that is an expression pattern independent of body weight regain. Expression of 71 of these genes correlated with measurements of adipocyte morphology or serum adipokine levels. CONCLUSION: The continuous improvement in WAT inflammatory gene expression, despite body weight relapse, may contribute to the sustained effects on adipose morphology after bariatric surgery.

Point-of-care oral cytology tool for the screening and assessment of potentially malignant oral lesions.

BACKGROUND: The effective detection and monitoring of potentially malignant oral lesions (PMOL) are critical to identifying early-stage cancer and improving outcomes. In the current study, the authors described cytopathology tools, including machine learning algorithms, clinical algorithms, and test reports developed to assist pathologists and clinicians with PMOL evaluation. METHODS: Data were acquired from a multisite clinical validation study of 999 subjects with PMOLs and oral squamous cell carcinoma (OSCC) using a cytology-on-a-chip approach. A machine learning model was trained to recognize and quantify the distributions of 4 cell phenotypes. A least absolute shrinkage and selection operator (lasso) logistic regression model was trained to distinguish PMOLs and cancer across a spectrum of histopathologic diagnoses ranging from benign, to increasing grades of oral epithelial dysplasia (OED), to OSCC using demographics, lesion characteristics, and cell phenotypes. Cytopathology software was developed to assist pathologists in reviewing brush cytology test results, including high-content cell analyses, data visualization tools, and results reporting. RESULTS: Cell phenotypes were determined accurately through an automated cytological assay and machine learning approach (99.3% accuracy). Significant differences in cell phenotype distributions across diagnostic categories were found in 3 phenotypes (type 1 ["mature squamous"], type 2 ["small round"], and type 3 ["leukocytes"]). The clinical algorithms resulted in acceptable performance characteristics (area under the curve of 0.81 for benign vs mild dysplasia and 0.95 for benign vs malignancy). CONCLUSIONS: These new cytopathology tools represent a practical solution for rapid PMOL assessment, with the potential to facilitate screening and longitudinal monitoring in primary, secondary, and tertiary clinical care settings.

Epigenetic regulation of diabetogenic adipose morphology.

OBJECTIVE: Hypertrophic white adipose tissue (WAT) morphology is associated with insulin resistance and type 2 diabetes. The mechanisms governing hyperplastic versus hypertrophic WAT expansion are poorly understood. We assessed if epigenetic modifications in adipocytes are associated with hypertrophic adipose morphology. A subset of genes with differentially methylated CpG-sites (DMS) in the promoters was taken forward for functional evaluation. METHODS: The study included 126 women who underwent abdominal subcutaneous biopsy to determine adipose morphology. Global transcriptome profiling was performed on WAT from 113 of the women, and CpG methylome profiling on isolated adipocytes from 78 women. Small interfering RNAs (siRNA) knockdown in human mesenchymal stem cells (hMSCs) was used to assess influence of specific genes on lipid storage. RESULTS: A higher proportion of CpG-sites were methylated in hypertrophic compared to hyperplastic WAT. Methylation at 35,138 CpG-sites was found to correlate to adipose morphology. 2,102 of these CpG-sites were also differentially methylated in T2D; 98% showed directionally consistent change in methylation in WAT hypertrophy and T2D. We identified 2,508 DMS in 638 adipose morphology-associated genes where methylation correlated with gene expression. These genes were over-represented in gene sets relevant to WAT hypertrophy, such as insulin resistance, lipolysis, extracellular matrix organization, and innate immunity. siRNA knockdown of ADH1B, AZGP1, C14orf180, GYG2, HADH, PRKAR2B, PFKFB3, and AQP7 influenced lipid storage and metabolism. CONCLUSION: CpG methylation could be influential in determining adipose morphology and thereby constitute a novel antidiabetic target. We identified C14orf180 as a novel regulator of adipocyte lipid storage and possibly differentiation.

Development of a cytology-based multivariate analytical risk index for oral cancer.

OBJECTIVES: The diagnosis and management of oral cavity cancers are often complicated by the uncertainty of which patients will undergo malignant transformation, obligating close surveillance over time. However, serial biopsies are undesirable, highly invasive, and subject to inherent issues with poor inter-pathologist agreement and unpredictability as a surrogate for malignant transformation and clinical outcomes. The goal of this study was to develop and evaluate a Multivariate Analytical Risk Index for Oral Cancer (MARIO) with potential to provide non-invasive, sensitive, and quantitative risk assessments for monitoring lesion progression. MATERIALS AND METHODS: A series of predictive models were developed and validated using previously recorded single-cell data from oral cytology samples resulting in a "continuous risk score". Model development consisted of: (1) training base classification models for each diagnostic class pair, (2) pairwise coupling to obtain diagnostic class probabilities, and (3) a weighted aggregation resulting in a continuous MARIO. RESULTS AND CONCLUSIONS: Diagnostic accuracy based on optimized cut-points for the test dataset ranged from 76.0% for Benign, to 82.4% for Dysplastic, 89.6% for Malignant, and 97.6% for Normal controls for an overall MARIO accuracy of 72.8%. Furthermore, a strong positive relationship with diagnostic severity was demonstrated (Pearson's coefficient = 0.805 for test dataset) as well as the ability of the MARIO to respond to subtle changes in cell composition. The development of a continuous MARIO for PMOL is presented, resulting in a sensitive, accurate, and non-invasive method with potential for enabling monitoring disease progression, recurrence, and the need for therapeutic intervention of these lesions.

Data Resource: Vascular Risk in Adult New Zealanders (VARIANZ) datasets.

INTRODUCTION: The Vascular Risk in Adult New Zealanders (VARIANZ) datasets contain a range of routinely-collected New Zealand health data relevant to cardiovascular disease (CVD) and related conditions. The datasets enable exploration of cardiovascular-related treatment, service utilisation, outcomes and prognosis. PROCESSES: Each dataset is constructed by anonymised individual-level linkage of eight national administrative health databases to identify all New Zealand adults aged ≥20 years who have recorded contact with publicly-funded New Zealand health services during a given year from 2006 onwards, when data quality is considered sufficient. DATA CONTENTS: Individual-level data for each VARIANZ dataset can include variables covering demography, dispensing of cardiovascular disease (CVD) preventive medications and prior hospitalisations for atherosclerotic CVD, heart failure, atrial fibrillation and diabetes. If required, VARIANZ datasets can be individually linked to follow-up national routinely collected health data in subsequent years, including all-cause mortality events and fatal/non-fatal CVD events, to create VARIANZ longitudinal cohorts. Bespoke linkage can also be undertaken to include other national and regional administrative health data such as non-CVD related hospitalisations in order to explore CVD comorbidities or novel risk factors. Furthermore, a subset of the VARIANZ datasets based on specific health contacts (such as CVD hospitalisations only) can also be identified, and some data can be requested for years prior to 2006. The New Zealand routinely-collected health databases used to construct the VARIANZ datasets do not capture primary care diagnostic classifications or certain CVD risk factor data such as smoking status, blood pressure or lipid profiles. CONCLUSION: The Vascular Risk in Adult New Zealanders (VARIANZ) datasets capture the majority of the New Zealand population in a given year and are available from 2006 onwards, or earlier than 2006 for some datasets based on specific health contacts. VARIANZ data can be used to explore a range of research questions regarding management, outcomes and prognosis for CVD.

Correction: Adding insult to injury: Ship groundings are associated with coral disease in a pristine reef.

[This corrects the article DOI: 10.1371/journal.pone.0202939.].

Adding insult to injury: Ship groundings are associated with coral disease in a pristine reef.

In 2013, the remote Tubbataha Reef UNESCO World Heritage Site, in the western Philippines, experienced two ship groundings within four months: the USS Guardian (USSG), a US military vessel, and the Min Ping Yu (MPY), an illegal Chinese fishing vessel. Here, we present the results of coral disease assessments completed two years post-grounding and recovery patterns monitored annually within these grounding sites. Site assessments were undertaken in three distinct zones: 'ground zero', where reef was scoured to its limestone base by direct ship impact; the 'impact border', containing surviving upright but damaged, abraded and fragmented colonies injured during ship movement; and undamaged 'control' sites, remote from the ship groundings but located on the same atoll. Coral diseases were dominated by white syndromes, and prevalence was an order of magnitude higher within the impact border zones than within the other zones two years after the events. Hard coral cover has steadily increased at a mean rate of 3% per year within the scoured USSG site at a rate comparable to control sites. In contrast, recovery has been negligible within the rubble-dominated MPY site, suggesting that substrate quality strongly influenced recovery processes such as recruitment, as larvae do not survive well on unstable substrates. Long-term recovery trajectories from these two grounding events appeared strongly influenced by movement of the ship during and after each event, and site-specific wave-influenced persistence of rubble and debris. High prevalence of coral disease among damaged but surviving colonies two years post-grounding suggested long-term impacts which may be slowing recovery and creating localized pockets of higher persistent disease prevalence than that of the surrounding population.

Proliferative leukoplakia: Proposed new clinical diagnostic criteria.

OBJECTIVE: We aimed to characterize proliferative verrucous leukoplakia (PVL) from a clinical and histopathological standpoint and suggest an updated classification. SUBJECTS AND METHODS: Records of patients seen at three oral medicine centers with a clinical diagnosis of PVL were reviewed for clinical and histopathological features and malignant transformation (MT). RESULTS: There were 42 patients (median age: 69 years [range: 36-88]; 35 females). 12.2% were current smokers. Family history of cancer was present in 43.7% of patients. Partial demarcation of lesion margins was present in 31.3% of lesions, followed by verrucous (27.5%), smooth (22.7%) erythematous (22.3%), and fissured (18.3%) appearance. Large and contiguous and multisite and non-contiguous lesions comprised 57.1% (24/42) and 35.7% (15/42) of PVL cases, respectively. 19.1% had prominent erythema (erythroleukoplakia). The most common histopathological diagnosis at first visit was hyperkeratosis without dysplasia (22/42; 56.4%). MT occurred in 71.4% patients after a median of 37 months [range: 1-210] from initial visit; erythroleukoplakia exhibited MT in 100% of cases. CONCLUSION: The generic term "proliferative leukoplakia (PL)" may be more appropriate than PVL because 18.3% were fissured and 22.7% erythematous. We also propose the term proliferative erythroleukoplakia to more accurately describe the subset of PL with prominent erythema, which had the highest MT rate.

Evidence-based clinical practice guideline for the evaluation of potentially malignant disorders in the oral cavity: a report of the American Dental Association

BACKGROUND: An expert panel convened by the American Dental Association (ADA) Council on Scientific Affairs and the Center for Evidence-Based Dentistry conducted a systematic review and formulated clinical recommendations to inform primary care clinicians about the potential use of adjuncts as triage tools for the evaluation of lesions, including potentially malignant disorders (PMDs), in the oral cavity. TYPES OF STUDIES REVIEWED: This is an update of the ADA's 2010 recommendations on the early diagnosis of PMDs and oral squamous cell carcinoma. The authors conducted a systematic search of the literature in MEDLINE and Embase via Ovid and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials and diagnostic test accuracy studies. The authors used the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty in the evidence and to move from the evidence to the decisions. RESULTS: The panel formulated 1 good practice statement and 6 clinical recommendations that concluded that no available adjuncts demonstrated sufficient diagnostic test accuracy to support their routine use as triage tools during the evaluation of lesions in the oral cavity. For patients seeking care for suspicious lesions, immediate performance of a biopsy or referral to a specialist remains the single most important recommendation for clinical practice. In exceptional cases, when patients decline a biopsy or live in rural areas with limited access to care, the panel suggested that cytologic testing may be used to initiate the diagnostic process until a biopsy can be performed (conditional recommendation, low-quality evidence). CONCLUSIONS AND PRACTICAL IMPLICATIONS: The authors urge clinicians to remain alert and take diligent action when they identify a PMD. The authors emphasize the need for counseling because patients may delay diagnosis because of anxiety and denial.(AU)

Functional strength training and movement performance therapy produce analogous improvement in sit-to-stand early after stroke: early-phase randomised controlled trial.

OBJECTIVES: Restoring independence in the sit-to-stand (STS) task is an important objective for stroke rehabilitation. It is not known if a particular intervention, strength training or therapy focused on movement performance is more likely to improve STS recovery. This study aimed to compare STS outcomes from functional strength training, movement performance therapy and conventional therapy. DESIGN: Randomised controlled trial. SETTING: Acute stroke units. PARTICIPANTS: Medically well patients (n=93) with recent (<42 days) stroke. The mean age of patients was 68.8 years, mean time post ictus was 33.5 days, 54 (58%) were male, 20 showed neglect (22%) and 37 (40%) had a left-sided brain lesion. INTERVENTIONS: Six weeks of either conventional therapy, functional strength training or movement performance therapy. Subjects were allocated to groups on a random basis. MAIN OUTCOME MEASURES: STS ability, timing, symmetry, co-ordination, smoothness and knee velocity were measured at baseline, outcome (after 6 weeks of intervention) and follow-up (3 months after outcome). RESULTS: No significant differences were found between the groups. All three groups improved their STS ability, with 88% able to STS at follow-up compared with 56% at baseline. Few differences were noted in quality of movement, with only symmetry when rising showing significantly greater improvement in the movement performance therapy group; this benefit was not evident at follow-up. CONCLUSIONS: Recovery of the STS movement is consistently good during stroke rehabilitation, irrespective of the type of therapy experienced. Changes in quality of movement did not differ according to group allocation, indicating that the type of therapy is less important. Clinical trial registration number NCT00322192.