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The text is a report on clinical imaging and electrophysiology in the field of Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Degeneration (FTD). It is authored by a large number of researchers from various institutions. The report provides a comprehensive overview of the current research and findings in the field, covering topics such as imaging techniques, electrophysiological measurements, and their applications in diagnosing and monitoring ALS and FTD. The report is a valuable resource for library patrons interested in understanding the latest advancements in clinical imaging and electrophysiology in ALS and FTD research. [Extracted from the article]

Spinal cord imaging in amyotrophic lateral sclerosis: historical concepts - novel techniques. Integrated magnetic resonance imaging and [11 C]-PBR28 positron emission tomographic imaging in amyotrophic lateral sclerosis. 1 Bashford J, Mills K, Shaw C. The evolving role of surface electromyography in amyotrophic lateral sclerosis: a systematic review. Comparison of Two Clinical Upper Motor Neuron Burden Rating Scales in ALS Using Quantitative Brain Imaging. [Extracted from the article]

• Fasciculation, myokymia and neuromyotonia are the core spontaneous phenomena of motor hyperexcitability. • Accurate characterisation is particularly important in amyotrophic lateral sclerosis, Isaacs syndrome and Morvan syndrome. • Advanced quantification by high-density surface electromyography could enhance biomarker development and therapeutic monitoring. Possessing a discrete functional repertoire, the anterior horn cell can be in one of two electrophysiological states: on or off. Usually under tight regulatory control by the central nervous system, a hierarchical network of these specialist neurons ensures muscular strength is coordinated, gradated and adaptable. However, spontaneous activation of these cells and their axons can result in abnormal muscular twitching. The muscular twitch is the common building block of several distinct clinical patterns, namely fasciculation, myokymia and neuromyotonia. When attempting to distinguish these entities electromyographically, their unique temporal and morphological profiles must be appreciated. Detection and quantification of burst duration, firing frequency, multiplet patterns and amplitude are informative. A common feature is their persistence during sleep. In this review, we explain the accepted terminology used to describe the spontaneous phenomena of motor hyperexcitability, highlighting potential pitfalls amidst a bemusing and complex collection of overlapping terms. We outline the relevance of these findings within the context of disease, principally amyotrophic lateral sclerosis, Isaacs syndrome and Morvan syndrome. In addition, we highlight the use of high-density surface electromyography, suggesting that more widespread use of this non-invasive technique is likely to provide an enhanced understanding of these motor hyperexcitability syndromes. [ABSTRACT FROM AUTHOR]

• Surface EMG offers significant practical advantages over invasive methods in ALS patients. • A variety of techniques exist to harness the superior spatial resolution of high-density surface EMG. • Multi-disciplinary collaboration is required to combat analytical and technical challenges. Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease that leads to inexorable motor decline and a median survival of three years from symptom onset. Surface EMG represents a major technological advance that has been harnessed in the development of novel neurophysiological biomarkers. We have systematically reviewed the current application of surface EMG techniques in ALS. We searched PubMed to identify 42 studies focusing on surface EMG and its associated analytical methods in the diagnosis, prognosis and monitoring of ALS patients. A wide variety of analytical techniques were identified, involving motor unit decomposition from high-density grids, motor unit number estimation and measurements of neuronal hyperexcitability or neuromuscular architecture. Some studies have proposed specific diagnostic and prognostic criteria however clinical calibration in large ALS cohorts is currently lacking. The most validated method to monitor disease is the motor unit number index (MUNIX), which has been implemented as an outcome measure in two ALS clinical trials. Surface EMG offers significant practical and analytical flexibility compared to invasive techniques. To capitalise on this fully, emphasis must be placed upon the multi-disciplinary collaboration of clinicians, bioengineers, mathematicians and biostatisticians. Surface EMG techniques can enrich effective biomarker development in ALS. [ABSTRACT FROM AUTHOR]

• A novel preprocessing step removes the need for manual selection of relaxed surface EMG data. • SPiQE provides reliable fasciculation analysis from raw thirty-minute recordings in ALS. • This paves the way for clinical calibration of a potential novel biomarker of disease progression. Fasciculations are a clinical hallmark of amyotrophic lateral sclerosis (ALS). The Surface Potential Quantification Engine (SPiQE) is a novel analytical tool to identify fasciculation potentials from high-density surface electromyography (HDSEMG). This method was accurate on relaxed recordings amidst fluctuating noise levels. To avoid time-consuming manual exclusion of voluntary muscle activity, we developed a method capable of rapidly excluding voluntary potentials and integrating with the established SPiQE pipeline. Six ALS patients, one patient with benign fasciculation syndrome and one patient with multifocal motor neuropathy underwent monthly thirty-minute HDSEMG from biceps and gastrocnemius. In MATLAB, we developed and compared the performance of four Active Voluntary IDentification (AVID) strategies, producing a decision aid for optimal selection. Assessment of 601 one-minute recordings permitted the development of sensitive, specific and screening strategies to exclude voluntary potentials. Exclusion times (0.2–13.1 minutes), processing times (10.7–49.5 seconds) and fasciculation frequencies (27.4–71.1 per minute) for 165 thirty-minute recordings were compared. The overall median fasciculation frequency was 40.5 per minute (10.6–79.4 IQR). We hereby introduce AVID as a flexible, targeted approach to exclude voluntary muscle activity from HDSEMG recordings. Longitudinal quantification of fasciculations in ALS could provide unique insight into motor neuron health. [ABSTRACT FROM AUTHOR]

• SPiQE combines serial high-density surface EMG with an innovative signal-processing methodology. • SPiQE identifies fasciculations in ALS patients with high sensitivity and specificity. • The optimal noise-responsive model achieves an average classification accuracy of 88%. Fasciculations are a clinical hallmark of amyotrophic lateral sclerosis (ALS). Compared to concentric needle EMG, high-density surface EMG (HDSEMG) is non-invasive and records fasciculation potentials (FPs) from greater muscle volumes over longer durations. To detect and characterise FPs from vast data sets generated by serial HDSEMG, we developed an automated analytical tool. Six ALS patients and two control patients (one with benign fasciculation syndrome and one with multifocal motor neuropathy) underwent 30-minute HDSEMG from biceps and gastrocnemius monthly. In MATLAB we developed a novel, innovative method to identify FPs amidst fluctuating noise levels. One hundred repeats of 5-fold cross validation estimated the model's predictive ability. By applying this method, we identified 5,318 FPs from 80 minutes of recordings with a sensitivity of 83.6% (+/− 0.2 SEM), specificity of 91.6% (+/− 0.1 SEM) and classification accuracy of 87.9% (+/− 0.1 SEM). An amplitude exclusion threshold (100 μV) removed excessively noisy data without compromising sensitivity. The resulting automated FP counts were not significantly different to the manual counts (p = 0.394). We have devised and internally validated an automated method to accurately identify FPs from HDSEMG, a technique we have named Surface Potential Quantification Engine (SPiQE). Longitudinal quantification of fasciculations in ALS could provide unique insight into motor neuron health. [ABSTRACT FROM AUTHOR]

We investigate the sequence-dependent behaviour of localised excitations in a toy, nonlinear model of DNA base-pair opening originally proposed by Salerno. Specifically we ask whether “breather” solitons could play a role in the facilitated location of promoters by RNA polymerase (RNAP). In an effective potential formalism, we find excellent correlation between potential minima and Escherichia coli promoter recognition sites in the T7 bacteriophage genome. Evidence for a similar relationship between phage promoters and downstream coding regions is found and alternative reasons for links between AT richness and transcriptionally-significant sites are discussed. Consideration of the soliton energy of translocation provides a novel dynamical picture of sliding: steep potential gradients correspond to deterministic motion, while “flat” regions, corresponding to homogeneous AT or GC content, are governed by random, thermal motion. Finally we demonstrate an interesting equivalence between planar, breather solitons and the helical motion of a sliding protein “particle” about a bent DNA axis. [ABSTRACT FROM AUTHOR]

Mantle cell lymphoma (MCL) is rarely cured with either conventional-dose chemotherapy or autografting. Recent evidence suggests that anti-CD20 monoclonal antibody therapy (rituximab) in combination with chemotherapy may improve the response rate. We report a pilot study of autografting using busulfan?–?melphalan conditioning followed by rituximab in 9 patients (median age 52 years) with chemosensitive MCL. Rituximab was given for 4 doses of 375?mg/m 2 between 4 and 10 weeks post-transplant. Three of 5 patients autografted after induction therapy remain alive in clinical and molecular complete remission at 33?–?50 months post-transplant. Only 1 of 4 patients autografted after relapse remains in complete remission. Two of the 3 patients with persistent marrow molecular positivity post-autograft became negative after rituximab therapy. Molecular negativity was first observed in 2 patients only after rituximab therapy. Overall, 2 patients have relapsed and the remaining 3 died of late-onset respiratory failure, probably reflecting infection and/or aggressive conditioning in an older patient population. These preliminary results, together with a review of the literature, suggest that the combination of autografting and rituximab may lead to durable molecular remissions in patients with chemosensitive MCL. Further studies are required to clarify whether the administration of rituximab: (1) is optimal pre- or post-autograft and (2) impacts on the incidence of infection and idiopathic pneumonitis in this context. [ABSTRACT FROM AUTHOR]

This study assessed the ability of recombinant human stem cell factor (rHuSCF) to mobilize stem cells in 44 patients who had failed a prior mobilization (CD34+ yield 0.5-1.9 x 106/kg BW) with filgrastim-alone or chemotherapy-plus-filgrastim. The same mobilization regimen was used with the addition of rHuSCF. In the filgrastim-alone group (n=13), rHuSCF 20?ug/kg was started 3 days before filgrastim and continued for the duration of filgrastim. In the chemotherapy-plus-filgrastim group (n=31), rHuSCF 20?ug/kg/day plus filgrastim 5-10?ug/kg/day were administered concurrently. Leukaphereses were continued to a maximum of four procedures or a target of ?3 x 106 CD34+ cells/kg. In both groups, CD34+ yield (x 106/kg BW) of the study mobilization was higher than that of the prior mobilization (median: 2.42 vs 0.84 P=0.002 and 1.64 vs 0.99 P=<0.001, respectively). In all 54 and 45% of patients in the filgrastim-alone group and chemotherapy-plus-filgrastim group, respectively, reached the threshold yield of 2 x 106/kg. The probability of a successful mobilization was the same in those with a CD34+ yield of 0.5-0.75 x 106/kg BW in the prior mobilization as in those with 0.76-1.99 x 106/kg BW. Downmodulation of c-kit expression and a lower percentage of Thy-1 positivity in the mobilized CD34+ cells were noted in the successful mobilizers compared with those in the poor mobilizers. This study shows that rhuSCF is effective in approximately half the patients who had failed a prior mobilization and allows them to proceed to transplant. It also points to the likely role of the SCF/c-kit ligand pair in mobilization.Bone Marrow Transplantation (2003) 31, 371-378. doi:10.1038/sj.bmt.1703860 [ABSTRACT FROM AUTHOR]

Background We have previously reported that repeated cycles of high-dose therapy (HDT), can be supported by unmanipulated autologous PBPC. Here we investigate whether purified CD34 + cells, obtained by immunomagnetic separation using the Isolex 300i device, can support such therapy. Methods Twenty-nine consecutive patients with metastatic breast cancer had PBPC mobilized and harvested following chemotherapy and G-CSF (10 µg/kg per day). Patients with > 4.0 × 10 6 /kg CD34, + cells in the apheresis product underwent CD34-selection using the Isolex 300i (v2.0) device. All cells collected were equally divided into three aliquots and cryopreserved. Patients who did not achieve this threshold had unmanipulated cells collected and stored. Patients subsequently received three cycles of HDT with paclitaxel (175 mg/m 2 ), thiotepa (300 mg/m 2 ) and either ifosfamide (10 g/m2) or cyclophosphamide (4 g/m 2 ). It was intended for patients to receive CD34-selected cells to support each of the three cycles of HDT (i.e 1/3 for each cycle) and to compare hemopoietic recovery between patients receiving CD34- selected cells or unmanipulated cells. Results Thirteen of the 29 patients (45%) did not mobilize sufficient CD34 + cells to undergo CD34-selection. The remaining 16 patients underwent CD34-selection with a median purity of 84.3% (range: 16.3-96.1%) and yield of 34% (range: 1-60%). Fifteen of these patients proceeded to HDT and 42 of the planned 45 cycles were administered. Nine patients had all three HDT cycles supported by CD34-selected cells. The median number of CD34-selected cells (× 10 6 /kg) infused per cycle was 1.5 (range: 0.04-3.01). Three of the 15 patients required infusion of 'back-up' unmanipulated cells because of delayed neutrophil recovery. Of the 13 patients whose PBPCs did not undergo CD34 + cell selection, 11 proceeded to HDT with a median of 3.2 × 10 6 /kg (range: 2.0-4.4) unselected cells infused per cycle and 31 of 33 planned cycles were delivered. When hemopoietic recovery was compared between cycles of HDT supported by CD34-selected (n = 34) and unmanipulated cells (n = 31), there was a modest slowing in the patients receiving CD34-selected cells; time to ANC > 1.0 × 10 9 /L = 11 days versus 10 days (P = 0.0122) and platelets > 20 × 109/L = 14 days versus 13 days (P = 0.0009). No difference in recovery to 50 × 10 9 /L was observed (P = 0.54). Conclusion We have demonstrated that Isolex 300i CD34-selected cells are capable of supporting multiple cycles of HDT. However, we were unable to acquire sufficient CD34 + cells to perform this processing in 45% (13/29) of patients and further improvements in yield are required to overcome the modest delay in neutrophil and platelet recovery. [ABSTRACT FROM AUTHOR]

Background : We have previously reported that repeated cycles of high-dose therapy (HDT), can be supported by unmanipulated autologous PBPC. Here we investigate whether purified CD34 + cells, obtained by immunomagnetic separation using the Isolex 300i device, can support such therapy. Methods : Twenty-nine consecutive patients with metastatic breast cancer had PBPC mobilized and harvested following chemotherapy and G-CSF (10 µg/kg per day). Patients with > 4.0 × 10 6 /kg CD34 + cells in the apheresis product underwent CD34-selection using the Isolex 300i (v2.0) device. All cells collected were equally divided into three aliquots and cryopreserved. Patients who did not achieve this threshold had unmanipulated cells collected and stored. Patients subsequently received three cycles of HDT with paclitaxel (175 mg/m 2 ), thiotepa (300 mg/m 2 ) and either ifosfamide (10 g/m 2 ) or cyclophosphamide (4 g/m 2 ). It was intended for patients to receive CD34-selected cells to support each of the three cycles of HDT (i.e 1/3 for each cycle) and to compare hemopoietic recovery between patients receiving CD34-selected cells or unmanipulated cells. Results : Thirteen of the 29 patients (45%) did not mobilize sufficient CD34 + cells to undergo CD34-selection. The remaining 16 patients underwent CD34-selection with a median purity of 84.3% (range: 16.3-96.1%) and yield of 34% (range: 1-60%). Fifteen of these patients proceeded to HDT and 42 of the planned 45 cycles were administered. Nine patients had all three HDT cycles supported by CD34-selected cells. The median number of CD34-selected cells (× 10 6 /kg) infused per cycle was 1.5 (range: 0.04-3.01). Three of the 15 patients required infusion of 'back-up' unmanipulated cells because of delayed neutrophil recovery. Of the 13 patients whose PBPCs did not undergo CD34 + cell selection, 11 proceeded to HDT with a median of 3.2 × 10 6 /kg (range: 2.0-4.4) unselected cells infused per cycle and 31 of 33 planned cycles were delivered. When hemopoietic recovery was compared between cycles of HDT supported by CD34-selected (n = 34) and unmanipulated cells (n = 31), there was a modest slowing in the patients receiving CD34-selected cells; time to ANC > 1.0 × 10 9 /L = 11 days versus 10 days (P = 0.0122) and platelets > 20 × 10 9 /L = 14 days versus 13 days (P = 0.0009). No difference in recovery to 50 × 10 9 /L was observed (P = 0.54). Conclusion : We have demonstrated that Isolex 300i CD34-selected cells are capable of supporting multiple cycles of HDT. However, we were unable to acquire sufficient CD34 + cells to perform this processing in 45% (13/29) of patients and further improvements in yield are required to overcome the modest delay in neutrophil and platelet recovery. [ABSTRACT FROM AUTHOR]

• 32 interventional clinical trials in ALS have employed at least one neurophysiological outcome measure. • The characteristics and experience of ten neurophysiological techniques used in these trials are summarised and evaluated. • Future trial design would benefit from a more standardised and refined neurophysiological toolkit. We collated all interventional clinical trials in amyotrophic lateral sclerosis (ALS), which utilised at least one neurophysiological technique as a primary or secondary outcome measure. By identifying the strengths and limitations of these studies, we aim to guide study design in future trials. We conducted and reported this systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eight databases were searched from inception. In total, 703 studies were retrieved for screening and eligibility assessment. Dating back to 1986, 32 eligible interventional clinical trials were identified, recruiting a median of 30 patients per completed trial. The most widely employed neurophysiological techniques were electromyography, motor unit number estimation (including motor unit number index), neurophysiological index and transcranial magnetic stimulation (including resting motor threshold and short-interval intracortical inhibition). Almost 40% of trials reported a positive outcome with respect to at least one neurophysiological measure. The interventions targeted either ion channels, immune mechanisms or neuronal metabolic pathways. Neurophysiology offers many promising biomarkers that can be utilised as outcome measures in interventional clinical trials in ALS. When selecting the most appropriate technique, key considerations include methodological standardisation, target engagement and logistical burden. Future trial design in ALS would benefit from a standardised, updated and easily accessible repository of neurophysiological outcome measures. [ABSTRACT FROM AUTHOR]

The article discusses Progressive multifocal leucoencephalopathy (PML) is a progressive and mostly fatal demyelinating disease caused by JC virus infection and destruction of infected oligodendrocytes in multiple brain foci of susceptible individuals.

• Aligned, automated outputs from muscle ultrasound and surface electromyography improved characterisation of fasciculations. • The latency between electrical and mechanical peaks was prolonged in amyotrophic lateral sclerosis. • Such insight into impaired excitation–contraction coupling could be translated into a novel biomarker of disease. In amyotrophic lateral sclerosis (ALS), motor neurons become hyperexcitable and spontaneously discharge electrical impulses causing fasciculations. These can be detected by two noninvasive methods: high-density surface electromyography (HDSEMG) and muscle ultrasonography (MUS). We combined these methods simultaneously to explore the electromechanical properties of fasciculations, seeking a novel biomarker of disease. Twelve ALS patients and thirteen healthy participants each provided up to 24 minutes of recordings from the right biceps brachii (BB) and gastrocnemius medialis (GM). Two automated algorithms (Surface Potential Quantification Engine and a Gaussian mixture model) were applied to HDSEMG and MUS data to identify correlated electromechanical fasciculation events. We identified 4,197 correlated electromechanical fasciculation events. HDSEMG reliably detected electromechanical events up to 30 mm below the skin surface with an inverse correlation between amplitude and depth in ALS muscles. Compared to Healthy-GM muscles (mean = 79.8 ms), electromechanical latency was prolonged in ALS-GM (mean = 108.8 ms; p = 0.0458) and ALS-BB (mean = 112.0 ms; p = 0.0128) muscles. Electromechanical latency did not correlate with disease duration, symptom burden, sum muscle power score or fasciculation frequency. Prolonged fasciculation electromechanical latency indicates impairment of the excitation–contraction coupling mechanism, warranting further exploration as a potential novel biomarker of disease in ALS. This study points to an electromechanical defect within the muscles of ALS patients. [ABSTRACT FROM AUTHOR]

While decision analysis has the potential to improve treatment decisions, the quality of patient specific data has hindered its development. Experience with the General Practice Research Database (GPRD) indicated the possibility of generating such data. The example developed concerns the probability of recurrent stroke and the risks and benefits of treatment with aspirin. Eight criteria were systematically applied to identify suitable patients from the 664,241 cohort of patients in the West Midlands GPRD. The risk of recurrent stroke was estimated using survival analysis, yielding multivariate hazard ratios for 960 patient profiles. These were used to populate a decision analysis model. The study highlights how decision analysis can introduce evidence-based information into the consultation. Data can be transformed into information for the increasingly complex world of general practice. This can clarify the risks and benefits of prescribing, assist GP--patient dialogue and promote shared decision-making. [ABSTRACT FROM AUTHOR]

Summary:The purpose of this investigation was to evaluate the impact of undertaking peripheral blood stem cell transplantation (PBST) on quality of life (QoL), and to determine the effect of participating in a mixed-type, moderate-intensity exercise program on QoL. It was also an objective to determine the relationship between peak aerobic capacity and QoL in PBST patients. QoL was assessed via the CARES questionnaire and peak aerobic capacity by a maximal graded treadmill test, pretransplant (PI), post transplant (PII) and following a 12-week intervention period (PIII). At PII, 12 patients were divided equally into a control or exercise intervention group. Undergoing a PBST was associated with a statistically but not clinically significant decline in QoL (P<0.05). Following the intervention, exercising patients demonstrated an improved QoL when compared with pretransplant ratings (P<0.01) and nonexercising transplant patients (P<0.05). Moreover, peak aerobic capacity and QoL were correlated (P<0.05). The findings demonstrated that exercise participation following oncology treatment is associated with a reduction in the number and severity of endorsed problems, which in turn leads to improvements in global, physical and psychosocial QoL. Furthermore, a relationship between fitness and QoL exists, with those experiencing higher levels of fitness also demonstrating higher QoL.Bone Marrow Transplantation (2004) 33, 553-558. doi:10.1038/sj.bmt.1704378 Published online 12 January 2004 [ABSTRACT FROM AUTHOR]

OBJECTIVE: To develop and evaluate in primary care a computerised decision support system for the management of stroke patients based upon 'patient profile decision analysis'. DESIGN: The decision support system incorporated the findings of 960 Markov models examining the decision to prescribe aspirin in the secondary prevention of stroke. The models reflected each combination of nine risk factors that determined a patient's profile. The evaluation comprised a qualitative interview and a questionnaire administered before and after the general practitioners (GPs) were given access to the support system. SETTING: Primary care. PARTICIPANTS: 15 GPs from the West Midlands. MAIN OUTCOME MEASURES: Decision certainty scoring of hypothetical patient vignettes. Qualitative perceptions of the applicability and acceptability of the system for primary care. RESULTS: After using the system, GPs were more certain of their decision making and made decisions more in line with national guidelines. Quantitative results further suggested that the system made decision making easier, improved feelings of being supported, improved the quality of decision making and increased satisfaction. Qualitative themes included that GPs thought the system could clarify their own decision making and improve GP-patient dialogue. CONCLUSIONS: The feasibility of individualised decision analysis for general practice has been questioned. Patient profile decision analysis, however, may be a valuable means of harnessing some of the advantages of the methodology to produce more patient-specific guidelines for primary care. [ABSTRACT FROM AUTHOR]

Adverse changes in nutrition-related outcomes including quality of life (QoL) occur after PBSC transplantation. This randomised controlled trial aims to evaluate the impact of nutrition and exercise counselling provided at hospital discharge on nutritional status, body composition and QoL post transplantation. Usual care (UC) (n=19) received no intervention after discharge; extended care (EC) (n=18) received fortnightly telephone counselling from a dietitian and exercise physiologist up to 100 days post transplantation. Nutritional status (patient-generated subjective global assessment, and diet history), QoL (EORTC QLQ-C30 version 3) and body composition (air displacement plethysmography) were assessed at pre-admission, discharge and 100 days post transplantation. Intervention groups were compared using two-sample t-tests of changes in the outcomes; results were adjusted using analysis of covariance. EC exhibited clinically important but not statistically significant increases in protein intake (14.7 g; confidence interval (CI) 95% −6.5, 35.9, P=0.165), cognitive functioning (7.2; CI 95% −7.9, 22.2, P=0.337) and social functioning (16.5; CI 95% −7.3, 40.3, P=0.165) compared with UC. Relative to pre-admission, EC experienced less weight loss than UC (−3.3 kg; CI 95% −6.7, 0.2, P=0.062). Physical activity was not significantly different between the groups. Ongoing nutrition and exercise counselling may prevent further weight loss and improve dietary intake and certain QoL components in autologous PBSC transplantation patients following hospitalisation. [ABSTRACT FROM AUTHOR]

Objective: To use the General Practice Research Database (GPRD) to explore the regional variation in prescribing for single diagnostic episodes of 'cough/cold' and sore throat and how this changed between 1993 and 2001. Methods: Data from the GPRD was used to conduct a longitudinal survey of morbidity and antibiotic prescribing data. Results: Nationally there has been a substantial reduction in diagnosed episodes per 1000 patient years at risk for both diagnoses: from 104.6 (104.0-105.2) to 86.5 (86.0-86.9) for cough/cold (-17.3%) and from 102.8 (102.2-103.4) to 69.2 (68.8-69.6) for sore throat (-32.6%), In addition to the changes in diagnostic rate there have been reductions in diagnosis-related prescribing: from 41.8% to 34.8% of cough/cold episodes (-7.0%) and from 77.3% to 60,8% of sore throat episodes (-16.4%). These aggregated data conceal wide regional variations. For cough/cold the change in prescribing rate during the study varied from 16.0% to +5.3% and for sore throat from -28.3% to -7.3%. Conclusions: In addition to a substantial reduction in diagnosis of cough/cold and sore throat, there has been a reduction in diagnosis-related prescribing episodes in almost all regions. Although there continues to be regional variation in diagnosis-related prescribing this has reduced substantially over the 9-year study period. [ABSTRACT FROM AUTHOR]

Summary:In this prospective multicentre trial, 90 patients undergoing autologous stem cell transplantation (ASCT) were randomised to receive (n=43) or not receive (n=47) amifostine 910?mg/m2 prior to melphalan 200?mg/m2. Patients were monitored for regimen-related toxicity, engraftment, supportive care, response and survival. Both groups underwent ASCT at a median of 8 months from diagnosis and were matched for disease characteristics, prior therapy and pre-ASCT disease responsiveness. Amifostine infusional side-effects were frequent, occurring in 65%of patients, but of mild severity. Amifostine use was associated with a reduction in the median grade of oral mucositis (1 vs 2, P=0.01) and the frequency of severe (WHO grades 3 or 4) mucositis (12 vs 33%, P=0.02), but no reduction in the requirement for parenteral nutrition or analgesic use. Conversion to complete remission post-ASCT occurred in 30 and 14%of the amifostine and control groups, respectively (P=0.09). With a median follow-up of 35 months, there was no statistically significant difference between the median progression-free or overall survival times for the two groups. We conclude that amifostine can be safely administered prior to high-dose melphalan and significantly reduces the frequency and severity of therapy-induced oral mucositis.Bone Marrow Transplantation (2005) 35, 971-977. doi:10.1038/sj.bmt.1704946 Published online 21 March 2005 [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the effect of peripheral blood stem cell transplantation on functional capacity, and to determine the role of a mixed type, moderate intensity exercise programme in the recovery of patients after intensive cancer treatment. Methods: Peak aerobic capacity and muscular strength (upper body, lower body, and handgrip strength) measures were assessed before (PI) and after (PII) transplant and after a 12 week intervention period (PIII). After PII, 12 patients aged 16-64 years were allotted in equal numbers to a control group or exercise intervention group. Results: Mean peak aerobic capacity and muscular strength were reduced after the transplant, with significant (p<0.05) decreases for upper body strength. No change was found in aerobic capacity and muscular strength between PII and PIII for the control group. In contrast, participation in the exercise programme led to significant improvements in peak aerobic capacity (p<0.0O5) and upper and lower body strength (p<0.01). In addition, values recorded after the three month intervention period were significantly higher than before treatment for peak aerobic capacity (litres/mm (p<0.05) and mI/kg/min (p<0.01)) and lower body strength (p<0.01). Conclusion: Intensive treatment for cancer can adversely affect aerobic capacity and muscular strength. A mixed type, moderate intensity exercise programme can help patients to regain fitness and strength within three months. No exercise can exacerbate physical losses resulting from treatment. [ABSTRACT FROM AUTHOR]

The purpose of this investigation was to assess changes in total energy expenditure (TEE), body weight (BW) and body composition following a peripheral blood stem cell transplant and following participation in a 3-month duration, moderate-intensity, mixed-type exercise programme. The doubly labelled and singly labelled water methods were used to measure TEE and total body water (TBW). Body weight and TBW were then used to calculate percentage body fat (%BF), and fat and fat-free mass (FFM). TEE and body composition measures were assessed pretransplant (PI), immediately post-transplant (PII) and 3 months post-PII (PIII). Following PII, 12 patients were divided equally into a control group (CG) or exercise intervention group (EG). While there was no change in TEE between pre- and post-transplant, BW (P<0.01) and FFM (P<0.05) significantly decreased during the same period. Participation in the exercise programme led to increases in TEE to levels that were both higher than pre- and post-transplant measures (P<0.01). By PIII, the exercising patients also showed gains in FFM (P<0.01) in association with a reduction in %BF (P<0.05). Exercise has a functionally important role in preserving and increasing skeletal mass in the rehabilitation phase of cancer patients.Bone Marrow Transplantation (2003) 31, 331-338. doi:10.1038/sj.bmt.1703867 [ABSTRACT FROM AUTHOR]

The Australian Leukaemia Study Group (ALSG) investigated whether G-CSF would accelerate haemopoietic recovery after induction treatment for acute myeloid leukaemia (AML) intensified with high-dose cytarabine, and therefore improve response rates and survival. Patients were randomised to receive lenograstim (glycosylated recombinant human G-CSF) 5 microg per kg body weight subcutaneously daily from day 8 after starting chemotherapy, or no cytokine, following chemotherapy with cytarabine 3 g/m2 every 12 h on days 1, 3, 5, and 7, together with idarubicin 9 or 12 mg/m2 on days 1, 2, and 3, plus etoposide 75 mg/m2 on days 1 to 7 inclusive. Patients had untreated AML, and were aged 16 to 60 years. Overall, 54 evaluable patients were randomised to receive lenograstim and 58 to no cytokine. Patients in the lenograstim arm had a significantly shorter duration of neutropenia <0.5 x 10(9)/l compared to patients in the no cytokine arm (median 18 vs 22 days; P = 0.0005), and also shorter duration of total leucopenia <1.0 x 10(9)/l (17 vs 19 days; P = 0.0002), as well as a reduction in duration of treatment with therapeutic intravenous antibiotics (20 vs 24 days; P= 0.015) and a trend to reduced number of days with fever >38.0 degrees C (9 vs 12 days; P = 0.18). There were no differences between the two groups in platelet recovery, red cell or platelet transfusions, or non-haematological toxicities. For patients achieving CR after their first induction course, a reduction in the time to the start of the next course of therapy was observed in the lenograstim arm, from a median of 40.5 days to a median of 36 days (P = 0.082). The overall complete response rates to chemotherapy were similar, 81% in the lenograstim arm vs 75% for the no cytokine arm (P = 0.5), and there was no significant difference in the survival durations. We conclude that the granulopoietic stimulating effect of G-CSF is observed after induction therapy for AML intensified by high-dose cytarabine, resulting in an improvement in a number of clinically important parameters with no major adverse effects. [ABSTRACT FROM AUTHOR]

In recent years the ratio of inhaled corticosteroid:bronchodilator (C:B) prescribing has been promoted as a quality marker for asthma treatment and cross-sectional data indicate an association with hospital admissions. If prescribing advice has been followed then it can be hypothesised that the C:B ratio will have increased and hospitalisation decreased. The West Midlands General Practice Research Database was used to monitor changes in the C:B ratio and hospital referrals for asthma between 1993 and 1996. The C:B ratio increased from 0.5 to 0.6 (P<0.001) and hospital referrals decreased from 7% to 4% per annum (P<0.001). Overall, 38% of the variation in hospital referrals was explained by the C:B ratio. This is higher than previous studies, perhaps because the study was longitudinal and the ratio assessed accurately in terms of volume rather than prescription items. When measured in defined daily doses, the C:B ratio does appear to have validity as an indicator of good prescribing in primary care. The General Practice Research Database offers an opportunity for assessing the validity of prescribing indicators before they are considered for wider use by Primary Care Groups and Health Authorities. [ABSTRACT FROM AUTHOR]