The effectiveness of peroneal nerve functional electrical simulation for the reduction of bradykinesia in Parkinson's disease: A feasibility study for a randomised control trial.

OBJECTIVES: To assess the feasibility of a multi-site randomised controlled trial to evaluate the effect of functional electrical stimulation on bradykinesia in people with Parkinson's disease. DESIGN: A two-arm assessor blinded randomised controlled trial with an 18 weeks intervention period and 4 weeks post-intervention follow-up. SETTING: Two UK hospitals; a therapy outpatient department in a district general hospital and a specialist neuroscience centre. PARTICIPANTS: A total of 64 participants with idiopathic Parkinson's disease and slow gait <1.25 ms-1. INTERVENTIONS: Functional electrical stimulation delivered to the common peroneal nerve while walking in addition to standard care compared with standard care alone. MAIN MEASURES: Feasibility aims included the determination of sample size, recruitment and retention rates, acceptability of the protocol and confirmation of the primary outcome measure. The outcome measures were 10 m walking speed, Unified Parkinson's Disease Rating Scale (UPDRS), Mini Balance Evaluation Systems Test, Parkinson's Disease Questionnaire-39, EuroQol 5-dimension 5-level, New Freezing of Gait questionnaire, Falls Efficacy Score International and falls diary. Participants opinion on the study design and relevance of outcome measures were evaluated using an embedded qualitative study. RESULTS: There was a mean difference between groups of 0.14 ms-1 (CI 0.03, 0.26) at week 18 in favour of the treatment group, which was maintained at week 22, 0.10 ms-1 (CI -0.05, 0.25). There was a mean difference in UPDRS motor examination score of -3.65 (CI -4.35, 0.54) at week 18 which was lost at week 22 -0.91 (CI -2.19, 2.26). CONCLUSION: The study design and intervention were feasible and supportive for a definitive trial. While both the study protocol and intervention were acceptable, recommendations for modifications are made.

Proton pump inhibitor associated hypomagnasaemia - a cause for concern?

AIMS: In recent years, there have been a number of case reports of severe hypomagnesaemia associated with proton pump inhibitor (PPI) use, such that both the FDA and MHRA have issued drug safety warnings. They have recommended periodic serum magnesium testing in patients prescribed PPIs but provide no guidance on timing of these measurements. METHODS: To our knowledge, we are the first to perform a prospective study to explore specifically proton pump inhibitor associated hypomagnesaemia (PPIAH). We followed 56 patients new to PPIs prospectively as well as a further 100 patients on long term PPIs cross-sectionally to identify what factors may be influencing the development of significant hypomagnesaemia. RESULTS: For the prospective arm of the study, we measured serum magnesium levels prior to starting a PPI and again at regular intervals for the next 8 months. For the cross-sectional arm of the study we measured serum magnesium levels on patients on PPI therapy ranging from less than 1 year to over 5 years. CONCLUSION: We found that, although there was a significant downward trend in serum magnesium levels in patients new to PPI therapy with time, clinically relevant hypomagnesaemia was not readily identifiable on regular blood testing. We did however identify patients on concurrent diuretic therapy as being at higher risk and so would recommend regular serum magnesium testing alongside their regular renal function monitoring on a more frequent basis such as annually.

How do absorbable sutures absorb? A prospective double-blind randomized clinical study of tissue reaction to polyglactin 910 sutures in human skin.

OBJECTIVE: To compare the tissue reaction produced by 2 gauges of implanted polyglactin 910(Vicryl) suture material in human skin. METHODS: A prospective, double masked, parallel randomized IRB approved clinical trial. Consecutive patients with involutional entropion and horizontal eyelid laxity were randomly allocated to 5/0 or 7/0 gauge test suture groups. Symptoms were alleviated during the wait for definitive surgery by placement of eyelid everting sutures. After 28 days, surgical entropion correction including eyelid wedge excision was achieved. Histological analysis was carried out, masked to the suture gauge used, on the excised eyelid containing one of the temporary everting sutures. Both patient and analyst were masked to the suture group. The four primary outcome measurements were granuloma outer diameter, central cellular diameter, giant cell number and area of fibrous coat and a statistical comparison made between suture gauge groups. RESULTS: 21 patients were allocated to each group, and histological analysis was possible in 36 patients. Significant suture-related granulomatous inflammatory reactions were found in all specimens. Medians of the measurements for 5/0 and 7/0 gauge sutures, respectively, were 0.855 mm versus 0.387 mm granuloma outer diameter (p = 0.0001); 0.464 mm versus 0.250 mm central cellular element diameter (p = 0.0003); 0.194 mm(2) versus 0.053 mm(2) fibrous coat area (p = 0.0009) and 0.8 versus 1.2 giant cell number (p = 0.7511). CONCLUSIONS: Polyglycolic acid sutures elicit a significant foreign body inflammatory response proportional to suture gauge. This reaction may be minimized by early suture removal. The study validates a novel and ethical approach to the examination of human skin response to implanted suture material.

The JAK2 46/1 haplotype predisposes to MPL-mutated myeloproliferative neoplasms.

The 46/1 JAK2 haplotype predisposes to V617F-positive myeloproliferative neoplasms, but the underlying mechanism is obscure. We analyzed essential thrombocythemia patients entered into the PT-1 studies and, as expected, found that 46/1 was overrepresented in V617F-positive cases (n = 404) versus controls (n = 1492, P = 3.9 x 10(-11)). The 46/1 haplotype was also overrepresented in cases without V617F (n = 347, P = .009), with an excess seen for both MPL exon 10 mutated and V617F, MPL exon 10 nonmutated cases. Analysis of further MPL-positive, V617F-negative cases confirmed an excess of 46/1 (n = 176, P = .002), but no association between MPL mutations and MPL haplotype was seen. An excess of 46/1 was also seen in JAK2 exon 12 mutated cases (n = 69, P = .002), and these mutations preferentially arose on the 46/1 chromosome (P = .029). No association between 46/1 and clinical or laboratory features was seen in the PT-1 cohort either with or without V617F. The excess of 46/1 in JAK2 exon 12 cases is compatible with both the "hypermutability" and "fertile ground" hypotheses, but the excess in MPL-mutated cases argues against the former. No difference in sequence, splicing, or expression of JAK2 was found on 46/1 compared with other haplotypes, suggesting that any functional difference of JAK2 on 46/1, if it exists, must be relatively subtle.

A randomised controlled trial of integrated electrical stimulation and physiotherapy to improve mobility for people less than 6 months post stroke.

PURPOSE: To investigate the feasibility of combining physiotherapy and functional electrical stimulation to improve gait post stroke. METHODS: A parallel group partially single-blinded randomised clinical trial. Adults living at home, less than 6 months post stroke, were randomised to Group A (physiotherapy, n = 10) or Group B (physiotherapy and common peroneal nerve stimulation, n = 10). Assessments were conducted before randomisation (Week 1), after intervention (Week 8) and after 12 weeks follow-up (Week 20). RESULTS: No between group differences were observed. There were statistically significant within group differences after the intervention period in both groups for walking speed and distance walked (without stimulation), Rivermead Mobility Index and Canadian Occupational Performance Measure, maintained at Week 20. There was statistically significant improvement in 10-m walking speed (Group B) when the stimulator was used at Week 8 (p = 0.03, median 0.04 m/s (8%)). Only Group B had statistically significant within group change in Rivermead Visual Gait Analysis (Week 8), maintained at Week 20. CONCLUSIONS: Integrating electrical stimulation and physiotherapy was feasible and improved walking speed. There was no evidence of a training effect compared with physiotherapy alone. One-hundred forty-four participants per group would produce an adequately powered study based on this protocol. Implications for Rehabilitation At the end of the intervention period participants using electrical stimulation to correct dropped foot walked faster. It was feasible for electrical stimulation to be combined with physiotherapy for people less than 6 months post stroke. A larger adequately powered study is required to establish whether there are training effects associated with use of stimulation in this population.

Diabetic peripheral microvascular complications: relationship to cognitive function.

Peripheral microvascular complications in diabetes are associated with concurrent cerebrovascular disease. As detailed cognitive assessment is not routinely carried out among diabetic patients, the aim was to establish whether the presence of clinical "peripheral" microvascular disease can identify a subgroup of patients with early evidence of cognitive impairment. Detailed psychometric assessment was performed in 23 diabetic patients with no microvascular complications (Group D), 27 diabetic patients with at least one microvascular complication: retinopathy, neuropathy, and/or nephropathy (Group DC), and 25 healthy controls (Group H). Groups D and DC participants had significantly lower scores on reaction time (P = 0.003 and 0.0001, resp.) compared to controls. Similarly, groups D and DC participants had significantly lower scores on rapid processing of visual information (P = 0.034 and 0.001, resp.) compared to controls. In contrast, there was no significant difference between Groups D and DC on any of the cognitive areas examined. The results show that diabetes, in general, is associated with cognitive dysfunction, but the additional presence of peripheral microvascular disease does not add to cognitive decline. The study, however, indirectly supports the notion that the aetiology of cognitive impairment in diabetes may not be restricted to vascular pathology.

Adverse effects reported in epilatory ruby laser treatment.

A retrospective study was conducted to investigate the incidence of reported adverse responses after epilatory laser treatment to control the growth of facial hair in patients with polycystic ovary syndrome. Forty-eight patients received a median of 6 (range 2-11) treatments with an Aesculap ruby laser during a 704 day monitoring period at Salisbury District Hospital. Nine adverse skin responses such as blistering, scabbing, sustained localised erythematous reactions or hyperpigmentation were reported. The energy output of the laser was also recorded at the start of every clinical session during this period using an external energy meter. The measured energy output of the laser was plotted alongside incidents of adverse responses, although no statistically significant correlation was found. The question of whether or not some adverse effects in ruby laser treatment can be attributed to laser performance remains open.

Blepharophimosis-ptosis-epicanthus inversus syndrome: objective analysis of surgical outcome in patients from a single unit.

BACKGROUND: The aim was to objectively assess surgical outcome in blepharophimosis-ptosis-epicanthus inversus syndrome (BPES). METHOD: Retrospective review of 14 consecutive patients with BPES. Mustardé double z plasty (at about age 4) and autogenous fascia lata Crawford brow suspension (9-12 months later) were used in all. One consultant performed all operations. Patient photographs were scanned and magnified for analysis. Preoperative and postoperative intercanthal distance, vertical palpebral aperture and cosmetic outcome were measured. Values were converted into ratios. RESULTS: Bilateral (mildly asymmetrical) ptosis and symmetrical epicanthic folds were found in all preoperatively. Seventy-one per cent had severe folds. Preoperative intercanthal distance ratio range was 1.26-1.60 (non-BPES=1.0). Median reduction post surgery was 26% (P=0.001, Wilcoxon's signed ranks test). Patients with largest preoperative ratio displayed greatest correction (P=0.029). Mustardé technique completely abolished all epicanthic folds and unmasked prominent caruncles in all. Fifty per cent had mild scarring postoperatively in the medial canthal region. Median change in marginal reflex distance ratio (right)=22.2% (P=0.012), left=18.2% (P=0.008), Wilcoxon's signed ranks tests. Postoperatively all had formed eyelid creases with improved upper lid position symmetry. CONCLUSIONS: This is the first known study objectively assessing surgical outcome in BPES. Mustardé double z plasty and Crawford autogenous fascia lata brow suspension are an effective surgical combination in the treatment of this syndrome, with overall cosmetic benefit.

Haemopoietic growth factors significantly improve the mitotic index and chromosome quality in cytogenetic cultures of myeloid neoplasia.

Haemopoietic growth factors stimulate bone marrow cell division, differentiation, and survival in vivo. We have investigated the use of recombinant human haemopoietic growth factors in vitro to improve cytogenetic cultures. Using a combination of granulocyte colony stimulating factor, granulocyte macrophage colony stimulating factor, stem cell factor, and interleukin-3, we developed an additive for bone marrow cultures intended to stimulate myeloid cell growth. Sixty-seven paired parallel cultures were analyzed, of which 50 were abnormal. The growth factor (GF) cultures showed a median four- to five-fold increase in mitotic index (MI) (P < 0.0001). In addition, the chromosome morphology was significantly improved in the GF cultures with a median increase in United Kingdom National External Quality Assessment Scheme quality score of 1.25 points (P < 0.0001). There was no statistically significant difference in the number of abnormal cells between the two culture methods. The combination of higher MI and improved chromosome quality substantially reduces the time required to process a case; furthermore, the GF medium is cheaper than the medium with which it was compared. This method is suitable for both diagnostic and follow-up cytogenetic analysis of acute and chronic myeloid neoplasia and is particularly useful for poorly cellular marrow samples or blood samples that would be expected to fail on standard culture. The use of this method has enabled substantial improvements in work efficiency in our oncology cytogenetic laboratory and reduced average reporting times from 9.0 days (2004/5) to 7.1 days (2005/6), despite a 6% increase in sample numbers.

Patterns and frequency of anxiety in women undergoing gynaecological surgery.

AIMS: Within a gynaecological surgical setting to identify the patterns and frequency of anxiety pre- and postoperatively; to identify any correlation between raised anxiety levels and postoperative pain; to identify events, from the patients' perspective, that may increase or decrease anxiety in the pre- and postoperative periods. BACKGROUND: It is well documented that surgery is associated with increased anxiety, which has an adverse impact on patient outcomes. Few studies have been conducted to obtain the patient's perspective on the experience of anxiety and the events and situations that aggravate and ameliorate it. METHOD: The study used a mixed method approach. The sample consisted of women undergoing planned gynaecological surgery. Anxiety was assessed using the State Trait Anxiety Inventory. Trait anxiety was measured at the time of recruitment. State anxiety was then assessed at six time points during the pre- and postoperative periods. Postoperative pain was also measured using a 10 cm visual analogue scale. Taped semi-structured telephone interviews were conducted approximately a week after discharge. RESULTS: State anxiety rose steadily from the night before surgery to the point of leaving the ward to go to theatre. Anxiety then increased sharply prior to the anaesthetic decreasing sharply afterwards. Patients with higher levels of trait anxiety were more likely to experience higher levels of anxiety throughout their admission. Elevated levels of pre- and postoperative anxiety were associated with increased levels of postoperative pain. Telephone interviews revealed a range of events/situations that patients recalled distressing them and many were related to inadequate information. CONCLUSION: This study found higher rates of anxiety than previously reported and anxiety levels appeared raised before admission to hospital. This has important clinical and research implications. RELEVANCE TO CLINICAL PRACTICE: Patients with high levels of anxiety may be identified preoperatively and interventions designed to reduce anxiety could be targeted to this vulnerable group. Patient experiences can inform the delivery of services to meet their health needs better.

Breakpoints of variant 9;22 translocations in chronic myeloid leukemia locate preferentially in the CG-richest regions of the genome.

From 5% to 10% of 9;22 translocations in chronic myeloid leukemia (CML) are reported to occur in variant form, that is, with the involvement of other regions of the genome in 3-way or more rearrangements. The literature indicates that the alternative breakpoints are not distributed randomly in the genome but show hotspots. We present data on 289 unpublished cases of CML with variant 9;22 translocations having a total of 342 variant breakpoints, the largest independent series to date. We found that the distribution of breaks was in loose agreement with the literature but that some new hotspots were identified; furthermore, some published hotspots were not fully supported by our data. Moreover, when our 342 variant breakpoints were plotted against profiles of CG heterogeneity in the genome, a significant positive correlation between breakpoint locations and CG composition was observed. In an ancillary study, we compared the frequency of variant t(9;22) with that of variants of t(15;17) associated with acute promyelocytic leukemia (AML M3). We found that the frequency of the former, 9.3%, was significantly higher than that of the latter, 2.6%.

Individual active treatment combined with group exercise for acute and subacute low back pain.

STUDY DESIGN: Randomized controlled trial. OBJECTIVE: To compare two fast-access evidence-based interventions for the treatment of simple low back pain. SUBJECTS: People aged 18-65 with a new episode of simple back pain causing them to be off work or on modified work for less than 1 year. SETTING: A district general hospital using a consultation/treatment room and a rehabilitation gym. METHODS: One group received a back advice booklet and one session of advice and then followed the normal route of care as directed by their general practitioner. The other group received the back booklet and one session of advice and also a back program. The back program consisted of a full assessment, immediately followed by one individual treatment, and then exercise classes over 1 to 2 weeks. OUTCOME MEASURES: (1) Rate of return to work, (2) pain scores and health status, and (3) cost effectiveness of interventions versus the financial cost to the individual or employer. RESULTS: On average, those receiving the individual treatment and group exercise took 7 days less off work. This represented a 35% reduction in the amount of time taken off work since study entry. The estimated cost saving of providing the extra service of a simple back program ranged between 250 pound (367 US dollars, 300 euro) and 578 pound (850 US dollars, 694 euro) for each patient. CONCLUSION: The results indicate that the costs of this active back program are more than reimbursed as a consequence of earlier return to work.

Effectiveness of electric stimulation of the vastus medialis muscle in the rehabilitation of patients after total knee arthroplasty.

OBJECTIVE: To investigate the possible effect of electric muscle stimulation (EMS) of the vastus medialis on the walking speed, Hospital for Special Surgery (HSS) knee score, and Physiological Cost Index (PCI) of patients during rehabilitation after total knee arthroplasty (TKA). DESIGN: Prospective, randomized controlled trial. SETTING: Various departments at a district general hospital in the United Kingdom. PARTICIPANTS: Thirty patients with unilateral osteoarthritis of the knee admitted for elective TKA were randomly assigned to 1 of 2 groups (15 per group): control and treatment. Both groups received standard physical therapy. The treatment group also received EMS of the vastus medialis. INTERVENTION: EMS (40Hz, 300micros) of the vastus medialis muscle for 4 hours a day, starting on postoperative day 2, over the first 6 postoperative weeks. MAIN OUTCOME MEASURES: Changes in walking speed, HSS knee score, and effort of walking as measured by the PCI. RESULTS: A statistically significant increase in walking speed was observed in the treatment group in relation to the control group at both 6 weeks (P=.0002) and 12 weeks (P<.0001) postoperatively. No statistically significant difference was observed in relation to the PCI or the HSS knee score variables. CONCLUSIONS: Application of EMS after TKA resulted in a statistically significant improvement in patients' walking speed. There was also a carry-over effect after the discontinuation of treatment.

A pilot study to investigate the combined use of botulinum neurotoxin type a and functional electrical stimulation, with physiotherapy, in the treatment of spastic dropped foot in subacute stroke.

The objective was to inform sample size calculations for a full randomized controlled trial (RCT). The design included an RCT pilot trial with a 16 week study period, including a 4 week baseline phase. The subjects were adults within 1 year of first stroke, ambulant with a spastic dropped foot. Twenty-one participants were recruited from the stroke services of 4 centers. For intervention all participants received physiotherapy; the treatment group also received botulinum neurotoxin Type A (BoNTA) intramuscular injections to triceps surae (800 U Dysport) and functional electrical stimulation (FES) of the common peroneal nerve to assist walking. The main outcome measure was walking speed. The result was a significant upward trend in median walking speed for both the control (p = 0.02) and treatment groups (nonstimulated p = 0.004, stimulated p = 0.042). Trend lines were different in location (p = 0.04 and p = 0.009, respectively). In conclusion, there is evidence of an additional, beneficial effect of BoNTA and FES. Sufficient information has been gained on the variability of the primary outcome measure to inform sample size calculations for a full RCT to quantify the treatment effect with precision.

The effect of combined use of botulinum toxin type A and functional electric stimulation in the treatment of spastic drop foot after stroke: a preliminary investigation.

OBJECTIVE: To investigate the effect of combined botulinum toxin type A (BTX) and functional electric stimulation (FES) treatment on spastic drop foot in stroke. DESIGN: Nonblinded randomized controlled trial. SETTING: Hospitals. PARTICIPANTS: Consecutive sample of 21 ambulant adults within 1 year after stroke with a spastic drop foot, of whom 18 completed the study. INTERVENTIONS: The treatment group received BTX injections (Dysport) on 1 occasion into the medial and lateral heads of the gastrocnemius (200U each) and tibialis posterior (400U each) muscles and FES, used on a daily basis for 16 weeks to assist walking. Both groups continued with physiotherapy at the same rate. MAIN OUTCOME MEASURES: Walking speed, Physiological Cost Index, Modified Ashworth Scale, Rivermead Motor Assessment, and Medical Outcomes Study 36-Item Short-Form Health Survey. RESULTS: Walking speed increased over 12 weeks in both control (P=.020) and treatment groups (nonstimulated, P=.004; stimulated, P=.042). The baseline corrected (analysis of covariance) increase in mean walking speed at 12 weeks, relative to controls, was.04m/s (95% confidence interval [CI],.003-.090) without stimulation, and.09m/s (95% CI,.031-.150) with stimulation. CONCLUSIONS: Combined treatment effectively improved walking and function. A larger study is needed to quantify the treatment effect and to investigate its impact on quality of life.

Economic and Practical Factors in Diagnosing HNPCC Using Clinical Criteria, Immunohistochemistry and Microsatellite Instability Analysis.

AIM: To determine a cost-efficient strategy for HNPCC molecular diagnostic testing. METHODS: 138 families referred to a Regional Genetics Service had hMLH1 and hMSH2 mutation analysis. The sensitivity and specificity of clinical selection criteria with or without immunohistochemistry (IHC) and microsatellite instability (MSI) analysis to further refine case selection and the effect of these approaches on the cost of mutation analysis were examined. RESULTS: Clearly deleterious mutations were identified in 49/138 (35.5%) of all families tested. The most sensitive criteria for identifying families with MMR mutations were the full Bethesda guidelines but these have poor specificity. IHC and MSI were useful pre-screening tools. CONCLUSION: A cost-efficient approach in laboratories where IHC and/or MSI analysis are available, is to use inclusive (non-specific) criteria to select cases, followed by IHC and then MSI. Where one or both results are abnormal, proceed to further mutation analysis. Where MSI or IHC or tumour blocks are not available, more restrictive clinical criteria may be more appropriate for cost-efficient case selection.