Droplet digital PCR quantification suggests that higher viral load correlates with improved survival in HPV-positive oropharyngeal tumours.

BACKGROUND: Although HPV-positive oropharyngeal cancer (OPC) patients have improved prognosis compared to HPV negative patients; there remains an HPV-positive group who have poor outcomes. Biomarkers to stratify discrete patient outcomes are thus desirable. Our objective was to analyse viral load (VL) by droplet digital PCR (ddPCR), in HPV-positive patients with OPC on whom clinical outcome data were available. METHODS: In a cohort of patients that had previously tested HPV positive via conventional PCR, VL was determined using ddPCR assays for HPV16 L1 and E6 genes. VL was classed as "medium/high" if more than 5.57 copies or 8.68 copies of the HPV 16 L1 or E6 gene were detected respectively. Effect of VL on overall survival and hazard of death & disease progression was performed with adjustments made for sex, age, deprivation, smoking, alcohol consumption and stage. RESULTS: L1 VL ranged from 0.0014-304 gene copies per cell with a mean of 30.9; comparatively E6 VL ranged from 0.0012-356 copies per cell with a mean of 37.9. Univariate analysis showed those with a medium/high VL had a lower hazard of death; this was significant for L1 (p = 0.02) but not for E6 (p = 0.67). The ratio of E6 to L1 deviated from n = 1 in most samples but had no influence on clinical outcomes. CONCLUSIONS: HPV viral load may be informative for the further stratification of clinical outcomes in HPV positive OPC patients.

Postoperative risk stratification in oral squamous cell carcinoma.

Postoperative prognostic stratification using the Union for International Cancer Control (UICC) TNM 8th edition staging rules (UICC 8) may identify additional groups of patients who could benefit from adjuvant radiotherapy. Currently, selection for such treatment is not based on all known prognostic factors, and their relative importance may vary depending on the overall risk category. The objective of this study therefore was to evaluate these possibilities. We retrospectively studied 644 patients who had surgery with curative intent for oral squamous cell carcinoma (OSCC) between March 2006 and February 2017. The outcomes of interest were disease-specific survival (DSS) and locoregional recurrence (LRR). Patients were re-staged according to the UICC 8 staging rules. Putative clinical and pathological prognostic variables were evaluated and hazard ratios estimated. Regression analysis was done to identify independent prognostic factors, and iterative analyses identified clinically-relevant risk categories with a minimum of residual prognostic variables. The significance of recognised pathological prognostic factors differed according to the overall risk category. An intermediate risk group comprising patients with pN1 disease as well those with pT3 disease solely on the basis of a depth of invasion (DOI) of more than 10 mm, was identified. A trial to evaluate the benefit or otherwise of adjuvant radiotherapy in this group is now required. Individual prognostic risk factors should be considered within the context of the overall risk category in patients with OSCC.

A Prospective Cohort Study of Human Papillomavirus-Driven Oropharyngeal Cancers: Implications for Prognosis and Immunisation.

AIMS: Oropharyngeal cancer (OPC) is increasing on a global scale, including the component driven by high-risk human papillomavirus (HR-HPV); contemporary data that provides insight into the prognosis of this disease in addition to the fraction attributable to HR-HPV are essential to inform primary and secondary disease management strategies. MATERIALS AND METHODS: A population-based cohort of 235 patients diagnosed with OPC between 2013 and 2015 in Scotland was assessed for HPV status using molecular genotyping. Associations between HR-HPV status and key clinical and demographic variables were estimated using the Pearson chi-squared test. Rates of overall survival and progression-free survival were estimated and visualised using Kaplan-Meier curves. RESULTS: HPV DNA (largely HPV 16) was identified in 60% of cases. After adjustment for age, gender, deprivation, smoking, alcohol consumption and tumour stage, patients with HR-HPV-positive OPC had an 89% reduction in the risk of death (hazard ratio = 0.11, 95% confidence interval 0.05-0.25) and an 85% reduction in the risk of disease progression (hazard ratio = 0.15, 95% confidence interval 0.07-0.30). HPV positivity was not associated with age, deprivation or smoking status, whereas those who reported excess alcohol consumption were less likely to be positive for HR-HPV. CONCLUSIONS: The prevalence of HR-HPV-associated OPC is high in Scotland and strongly associated with dramatically improved clinical outcomes, including survival. Demographic/behavioural variables did not reliably predict HPV positivity in this cohort, which underlines the importance of laboratory confirmation. Finally, the dominance of HPV 16 in OPC indicates the significant impact of prophylactic immunisation on this disease.

Is the 8th edition of the Union for International Cancer Control staging of oral cancer good enough?

Depth of invasion is an important predictor of survival. A study by the International Consortium (ICOR) for Outcome Research proposed incorporation of it (together with the greatest surface dimension, or the anatomical criteria, or both) into the T stage. This has been adopted in part by the 8th edition of the Union for International Cancer Control (UICC) TNM 8 classification of malignant tumours for oral squamous cell carcinoma (SCC). Our aim was to verify depth of invasion as an independent prognostic factor, and to validate the staging by comparing it with that specified in the 7th edition (TNM 7) and the T-staging model proposed by the International Consortium. We retrospectively studied 449 patients who had had operations for a previously untreated primary oral cancer between 2006 and 2014 at a single centre, and analysed the independent predictive value of depth of invasion for both disease-specific and overall survival. It was an independent predictor of disease-specific survival as were sex, perineural invasion, and N stage. It was also an independent predictor of overall survival together with sex and N status. Staging in TNM 8 gave a better balance of distribution than that in TNM 7, but did not discriminate between prognosis in patients with T3 and T4 disease. The proposed International Consortium rules for T-staging gave an improved balance in distribution and hazard discrimination. The incorporation of depth of invasion into the T-staging rules for oral SCC improved prognostic accuracy and is likely to influence the selection of patients for adjuvant treatment. Our findings suggest that the TNM 8 staging lacks hazard discrimination in patients with locally-advanced disease because its T4 staging is restricted to anatomical criteria.

Travel-related disseminated Penicillium marneffei infection in a renal transplant patient.

Penicillium marneffei is a thermally dimorphic fungus that causes severe human immunodeficiency virus-related opportunistic infection in endemic areas of Southeast Asia and has rarely been reported in solid organ transplant (SOT) recipients. We report here the case of an Australian renal transplant patient who presented with disseminated P. marneffei infection shortly after a 10-day holiday to Vietnam, and review all previously published cases of penicilliosis associated with renal transplantation. This is the first reported case, to our knowledge, of P. marneffei infection in an SOT recipient acquired during travel to an endemic country, and highlights the importance of an accurate travel history when opportunistic infection is suspected, as well as giving appropriate health advice to transplant patients who travel.

Squamous cell carcinoma of the thyroid gland: primary or secondary disease?

OBJECTIVE: To review the aetiopathogenesis, clinical characteristics, immunohistochemical profile, prognosis and treatment options for primary thyroid squamous cell carcinoma, and to compare it with squamous cell carcinoma metastatic to the thyroid, thus providing the reader with a framework for differentiating primary and secondary disease. METHOD: Review of English language literature from the past 25 years. SEARCH STRATEGY: A search of the Medline, Embase and Cochrane databases (April 1984 to April 2009) was undertaken to enable a comprehensive review. RESULTS: After applying strict criteria for the diagnosis of primary thyroid squamous cell carcinoma, 28 articles were identified reporting 84 cases. When reviewing secondary thyroid squamous cell carcinoma, we only analysed cases of squamous cell carcinoma metastatic to the thyroid gland, and found 28 articles reporting 78 cases. CONCLUSION: It is possible to differentiate between primary and secondary thyroid squamous cell carcinoma, on the basis of combined evidence from clinical examination and endoscopic, pathological and radiological evaluation. Such differentiation is important, as the prognosis for primary squamous cell carcinoma is uniformly poor irrespective of treatment, and the most suitable option may be supportive therapy. Treatment for secondary squamous cell carcinoma of the thyroid varies with the site and extent of spread of the primary tumour.

Outbreak of invasive methicillin-resistant Staphylococcus aureus infection associated with acupuncture and joint injection.

OBJECTIVE: To describe an outbreak of invasive methicillin-resistant Staphylococcus aureus (MRSA) infection after percutaneous needle procedures (acupuncture and joint injection) performed by a single medical practitioner. SETTING: A medical practitioner's office and 4 hospitals in Perth, Western Australia. PATIENTS: Eight individuals who developed invasive MRSA infection after acupuncture or joint injection performed by the medical practitioner. METHODS: We performed a prospective and retrospective outbreak investigation, including MRSA colonization surveillance, environmental sampling for MRSA, and detailed molecular typing of MRSA isolates. We performed an infection control audit of the medical practitioner's premises and practices and administered MRSA decolonization therapy to the medical practitioner. RESULTS: Eight cases of invasive MRSA infection were identified. Seven cases occurred as a cluster in May 2004; another case (identified retrospectively) occurred approximately 15 months earlier in February 2003. The primary sites of infection were the neck, shoulder, lower back, and hip: 5 patients had septic arthritis and bursitis, and 3 had pyomyositis; 3 patients had bacteremia, including 1 patient with possible endocarditis. The medical practitioner was found to be colonized with the same MRSA clone [ST22-MRSA-IV (EMRSA-15)] at 2 time points: shortly after the first case of infection in March 2003 and again in May 2004. After the medical practitioner's premises and practices were audited and he himself received MRSA decolonization therapy, no further cases were identified. CONCLUSIONS: This outbreak most likely resulted from a breakdown in sterile technique during percutaneous needle procedures, resulting in the transmission of MRSA from the medical practitioner to the patients. This report demonstrates the importance of surveillance and molecular typing in the identification and control of outbreaks of MRSA infection.

Recruitment to a clinical trial from the databases of specialists in Parkinson's disease.

BACKGROUND: Many clinical trials involving elderly people living at home suffer from low recruitment. We report our experience of recruiting people with Parkinson's disease (PD) from specialist clinical databases, to a randomised controlled trial of personalized exercise. METHODS: We aimed to recruit 200 repeat fallers with PD. Subjects were recruited through the clinical registers of specialists in PD in two NHS trusts. They had to have a confirmed diagnosis of PD, be independently mobile, live in the community, be a repeat faller, and were screened for cognitive impairment. RESULTS: Out of 1107 patients on the registers, 457 did not meet the eligibility criteria for the trial. A further 151 were excluded for other reasons. Four hundred and ninety-nine were approached to have a home screening visit: 405 replied and 305 agreed to be screened for the trial. Of those screened, 126 were non-repeat fallers and 22 failed other eligibility criteria. Out of the remaining 157 patients, 18 (11%) decided not to participate in the trial which left 139 recruited to the trial. Seven more were recruited from a second screen of previous non-repeat fallers. In total 146 patients were recruited: 142 to the main trial and four to the initial pilot phase. CONCLUSION: The percentage of patients who participated in the main trial was only 13% (95% confidence interval 11% to 15%) of those on specialists' registers, considerably less than estimated, although the proportion of fallers and repeat fallers was similar to that previously reported.

Renal biopsy in congenital ureteropelvic junction obstruction: evidence for parenchymal maldevelopment.

The renal histologic changes associated with congenital ureteropelvic junction obstruction (UPJO) and the relationship to clinical imaging have not been well studied. In order to better understand the histologic alterations of congenital UPJO and their relationship with clinical imaging and outcomes, we examined renal biopsies from 61 patients undergoing pyeloplasty for congenital UPJO. Glomeruli were analyzed for various injury patterns and the tubulointerstitium was examined for tubular atrophy/simplification and fibrosis. Two methods were used to evaluate tubular mass: glomerular density and morphometric measurement of tubular size and density. Control specimens were obtained from age-matched autopsy specimens without renal pathology. Glomerular changes were identified in 73% of all biopsies and were present in a range from 1.7 to 91% of glomeruli in each patient. Overt tubulointerstitial changes were present in 26% of all biopsies. Fibrosis was noted to occur with tubulointerstitial changes in a significantly greater fraction of children over the age of 1 year (P=0.026). Increased glomerular density was associated with severe hydronephrosis (P<0.02). Normal glomerular density was inversely correlated with age (P<0.001), but this relationship was more variable in UPJO (P<0.01). Among patients with intact differential function preoperatively (>45%), postoperative functional decline was predicted only by increased glomerular density. 20 biopsies without overt tubulointerstitial changes were analyzed morphometrically and showed a significant reduction in proximal tubular (PT) size, but unchanged density. Distal tubular (DT) size was unchanged in UPJO, but density was increased. The PT/DT ratio was therefore markedly decreased in UPJO (P<0.0001). Both PT and DT sizes were significantly larger in children with a diuretic renogram washout time less than 20 min than those with greater than 20 min, a common threshold for functionally significant obstruction (P<0.05). Capsular thickness was significantly increased in UPJO. In all, 36% of biopsies had a thickness >0.5 mm and this was associated with greater degrees of tubulointerstitial changes and glomerular alterations. Congenital UPJO produces a variety of renal parenchymal changes, which may in part reflect abnormal development. Some of these alternations are seen in clinical imaging and may help predict outcomes, but there is significant discordance between conventional imaging and histological findings.

Use and limitations of imatinib mesylate (Glivec), a selective inhibitor of the tyrosine kinase Abl transcript in the treatment of chronic myeloid leukaemia.

Chronic myeloid leukaemia is associated with a specific translocation between chromosomes 9 and 22 that results in the formation of a chimaeric gene. This gene, when transcribed, produces the BCR-Abl oncoprotein which has tyrosine kinase activity and the ability to prevent apoptosis, but has no effect on cellular proliferation. Imatinib mesylate, an inhibitor of the BCR-Abl transcript modelled on the ATP binding pocket of the Abl oncoprotein, prevents phosphorylation of effector molecules and induces apoptosis. Imatinib has limited effectiveness when BCR-Abl cells are in the quiescent cell-cycle state of G0. A life-long regimen of imatinib should reduce the risk of relapse from cells leaving G0. Up-regulation of BCR-Abl expression, ATP binding pocket mutations, up-regulation of MDR1 and over-expression of Pgp are all thought to limit the effectiveness of imatinib. Advanced BCR-Abl positivity is associated with complex mutations, which are thought to have a cumulative effect on the BCR-Abl oncoprotein in disrupting normal signal transduction, making these cells refractory to monotherapy alone. Combination therapy is thought to overcome this. Research studies have identified imatinib as a potential treatment option for a diverse range of malignancies associated with BCR-Abl, platelet-derived growth factor receptor (PDGFr) and c-Kit pathways. This may extend the application of this special therapy in the future.

Assessing and intervening on OSH programmes: effectiveness evaluation of the Wellworks-2 intervention in 15 manufacturing worksites.

AIMS: (1) To develop a transparent and broadly applicable method for assessing occupational safety and health (OSH) programmes or management systems; (2) to assess OSH programmes in a sample of manufacturing worksites; and (3) to determine whether a management focused occupational health intervention results in greater improvement in OSH programmes compared to minimal intervention controls. METHODS: OSH programmes were assessed using an adaptation of the US Occupational Safety & Health Administration's 1995 Program Evaluation Profile. Scores were generated from 91 binary indicator variables grouped under four "Essential Elements". Essential Element scores were weighted to contribute to an overall programme score on a 100 point scale. Seventeen large manufacturing worksites were assessed at baseline; 15 sites completed the 16 month intervention and follow up assessments. RESULTS: There was considerable variation in Essential Element scores across sites at baseline as judged by our instrument, particularly in "management commitment and employee participation" and "workplace analysis". Most sites scored highly on "hazard prevention and control" and "training and education". For overall OSH programme scores, most sites scored in the 60-80% range at baseline, with four sites scoring below 60%, suggesting weak programmes. Intervention sites showed greater improvements than controls in the four programme elements and in overall programme scores, with significantly greater improvements in "management commitment and employee participation". CONCLUSIONS: The OSH programme assessment method used is broadly applicable to manufacturing work settings, and baseline profiles suggest needs for improvement in OSH programmes in most such worksites. Despite a small sample size, results showed that sustained management focused intervention can result in improvement in these OSH programme measures.

Inferior turbinate reduction in children using Holmium YAG laser-a clinical and histological study.

BACKGROUND AND OBJECTIVES: To compare the efficacy and safety of inferior turbinate reduction in children using Holmium:YAG (Ho:Yag) laser and diathermy. Histological effects of these treatments on turbinate tissue are also studied. STUDY DESIGN/MATERIALS AND METHODS: A retrospective review and structured telephone interview of paediatric cases treated with Ho:Yag laser and diathermy to inferior turbinates. The complications, morbidity and efficacy were quantified. Histological sections of inferior turbinates treated with diathermy (surface and submucosal) and laser were compared. RESULTS: Efficacy in the laser (n = 8) and diathermy group (n = 11) was similar. The complication/morbidity score was lower in the laser group, 1.92 versus 3.48, (P = 0.04, CI: 0.01, 2). Long-term benefit was 50 and 36% in the laser and diathermy group respectively. Histology showed very limited tissue damage in all methods of treatment. CONCLUSIONS: Ho:Yag laser treatment is equally efficacious, but causes less complications and morbidity compared to surface diathermy. Both treatment methods have poor long-term efficacy, which may be related to limited tissue damage.

Phenotypic heterogeneity in pediatric autosomal dominant polycystic kidney disease at first presentation: a single-center, 20-year review.

BACKGROUND: The presentation of autosomal dominant polycystic kidney disease (ADPKD) in childhood provides an insight into comorbidities and potential areas for interventions and investigation. METHODS: Phenotypic heterogeneity at the time of first presentation was studied with respect to age of diagnosis, mode of presentation, parental inheritance pattern, renal function, associated hypertension, and hyperlipidemia. Fifty-five children (median age of presentation, 8.7 years; 27% < 1 year) with ADPKD from 44 families followed up between March 1983 and March 2003 were reviewed. The diagnosis was based on family history and ultrasound confirmation of cysts. Progression of renal disease was followed over the study period (mean duration of follow-up, 4.9 years). RESULTS: A family history of ADPKD was known at presentation in 89%, which precipitated the screening diagnostic imaging in 59% of these children. Maternal inheritance was displayed in 51%, whereas 5% had no known family history of ADPKD. Bilateral renal findings were present in 78%. Hypertension (>95(th) percentile for age) was present in 22%, and hyperlipidemia was present in 54%. Renal function was not significantly diminished in 98% of patients with creatinine clearance > or =3rd percentile for age, and 7% had persistent proteinuria (>150 mg/d). No subjects had hepatic, splenic, or pancreatic cysts on ultrasound scan. A subpopulation of 10 patients had features of ADPKD dating back to prenatal ultrasound scans. All prenatal cases were characterized by bilateral renal findings, 90% had a known family history of ADPKD at the time of presentation, and 89% of these patients displayed maternal inheritance. Follow-up studies showed a persistence of hyperlipidemia despite pharmacotherapeutic treatment of hypertension, infrequent proteinuria, and sustained renal function in most patients. CONCLUSION: The results of this study show that many children at the time of first presentation have a significant prevalence of modifiable risk factors: hypertension, proteinuria, and hyperlipidemia, in the face of normal renal function. The results also show a unique presentation existing in prenatal subjects.

A study to evaluate the met and unmet needs of members belonging to Young Stroke groups affiliated with the Stroke Association.

PURPOSE: To examine the met and unmet needs of young people with stroke who accessed services run by the Stroke Association. METHODS: One hundred and thirty-five out of 200 members of 14 participating Young Stroke groups completed and returned the postal version of the Southampton Needs Assessment Questionnaire for Stroke questionnaire. RESULTS: Young Stroke group members had a median of five unmet needs. An analysis of these needs showed that information about the person's stroke, help with finances, assistance with non-care activities (e.g. help with social activities) and help with maintaining intellectual fulfilment were the four most frequently reported ones. There was no association between the number of unmet needs reported and factors such as age, time since stroke and social class. CONCLUSIONS: Young Stroke group members may be more aware of what their unmet needs are and have better knowledge in accessing existing health and social service resources. Nevertheless, these findings show that people with stroke considered the provision of information geared to their own needs as important. Statutory services should personalize information to individual's specific situation and should also tackle other problems, not only physical ones, experienced by young people with strokes.

The unmet needs of young people who have had a stroke: results of a national UK survey.

BACKGROUND: Most stroke-related studies have consisted of people over the age of 65. This study examined the unmet needs of young people with stroke, living in community housing in the UK. METHOD: People with a stroke (>1 year ago), in two age bands (18-45; 46-65) were sent the Southampton Needs Assessment Questionnaire for people with Stroke. RESULTS: 315 out of 639 (49%) questionnaires were returned (mean age 55, SD 9; 189 males, 126 females). The median number of unmet needs reported was two (IQR 0-6). The most frequently reported unmet needs were: provision of information about the responders' stroke (45%); assistance with finances (24%); non-care activities (19%); and intellectual fulfillment (17%). Responders in the younger age group reported significantly more unmet needs than responders in the older age group (for a holiday, intellectual fulfillment and family support). Responders with poor mobility reported significantly more unmet needs than responders with average and good mobility for 15 unmet needs (three most pressing: respite care/short breaks; adaptations; and access to community environment). Responders who did not return to work reported significantly more unmet needs than responders who had reduced hours or changed jobs and people who returned to the same job with the same hours for seven unmet needs (three most pressing: help with finances; a holiday and speech therapy). CONCLUSION: People of younger age, with poorer mobility and those unable to return to work, report most unmet needs. Further work needs to be done within the community, with employers and professionals, in relation to education and the provision of specifically targeted information in order to facilitate participation and autonomy for people with stroke.

Transferring people safely with manual handling equipment.

OBJECTIVE: To determine whether transferring equipment designed to assist a carer when moving someone who is able to take some weight through their legs is likely to affect the risk of back problems in the carer. DESIGN: Twelve pieces of equipment were tested by nurses transferring patients from commode to wheelchair and vice versa, and from wheelchair to bed and vice versa. Video recordings were taken of each transfer and freeze-frame pictures at the moment of greatest load were analysed. Compressive disc force was deduced, using a biomechanical model, from the weights of the patient and nurse and measurements of anatomical distances and angles. SETTING: The Sir Walter Puckey Gait Laboratory, in the Rehabilitation Research Unit, University of Southampton. SUBJECTS: Six female trained nurses with no recent history of hernia, back pain or pregnancy during the previous six months were recruited to use the equipment. Two female patients were chosen from those volunteering and screened for stroke, confusion and unusual footwear. The patients were able to partially weight-bear and were used to being transferred. RESULTS: The results indicate that the critical value of 3.4 kN at the L5/S1 disc (specified by the US National Institute for Occupational Safety and Health) was not exceeded when using transferring equipment. CONCLUSION: In this study, loading on the spine during transferring tasks with or without equipment was not considered harmful when good technique was employed.

The effects of increased rehabilitation therapy after brain injury: results of a prospective controlled trial.

OBJECTIVE: The objective was to investigate the effect of increased intensity of rehabilitation therapy provided to brain-injured subjects on the rate at which independence was regained and the duration of hospital admission. DESIGN: A two-centre, prospective, controlled study with random allocation to groups. SETTING: Two district general hospitals on the south coast of England. SUBJECTS: Fifty-six people with moderate and severe head injury consecutively admitted to Southampton and Poole hospitals between June 1995 and September 1997. INTERVENTIONS: Increased intensity of rehabilitation therapy input without change in content. RESULTS: Subjects receiving more intensive therapy made more rapid progress and were discharged home sooner. The different intensities of therapy employed in this study showed no evidence of a 'ceiling' effect and the 'intervention group' made significantly more rapid progress on tests of dependency during the period of admission. A clear response to increased therapy input was seen in one of the centres with more rapid functional improvement and a shorter length of hospital stay. This centre already had more therapy and better community facilities. No such benefits were seen at the other centre where the intervention group had a longer hospital stay than the routine group. CONCLUSION: Increasing the hours per week of therapy given to adults recovering from brain injury in hospital can accelerate the rate of recovery of personal independence and result in their being discharged from hospital sooner. Increased rehabilitation therapy after brain injury is associated with enhanced functional recovery and shorter hospital stay if provided in the context of an integrated service that can provide ongoing community support. There is no evidence of any ceiling effect of therapeutic intensity beyond which no further response is observed.

Indices to describe different muscle activation patterns, identified during treadmill walking, in people with spastic drop-foot.

This study was concerned with individuals who were unable to effectively dorsiflex their ankle when walking, as a result of a lesion of the central nervous system (CNS). Indices that categorise and quantify different patterns of calf and anterior tibial muscle activation patterns during treadmill walking have been derived from a sample of fifteen individuals with established hemiplegia following stroke and twelve age-matched individuals without impairment. As subjects walked on a treadmill, force sensitive foot-switches under the heel and first metatarsal head allowed EMG signals from the calf and anterior tibial muscles to be related to phases of the gait cycle. Normal activation periods for each muscle group were identified as percentiles of the gait cycle and indices for muscle activation periods were derived using ratios of integrated EMG during selected periods. Indices were derived that identified statistically significant differences, between normal and hemiplegic subjects, in calf activation during both push-off phase (P<0.001) and early stance phase (P<001), but not activation of tibialis anterior during swing (P=0.325) Observation suggested that integrated tibialis anterior activity during swing phase in hemiplegic subjects was not dissimilar to normal subjects, but the profile in hemiplegic subjects tended to lack the normal second peak of activity at initial foot contact. The reasons for drop-foot were shown to be varied and complex. The indices defined may be useful for directing therapy and measuring outcome.