Thymopoiesis following HSCT; a retrospective review comparing interventions for aGVHD in a pediatric cohort.

Acute graft-versus-host disease (aGVHD) complicates allogeneic hematopoietic stem cell transplantation (HSCT), and is treated with topical and/or systemic corticosteroids. Systemic corticosteroids and aGVHD damage thymic tissue. We compared thymopoietic effect of topical steroid therapy, corticosteroids and extracorporeal photopheresis (ECP) in 102 pediatric allogeneic HSCT patients. We categorized patients into 4 groups: - no aGVHD, aGVHD treated with topical or systemic steroid, or ECP. Naïve CD4+CD45RA+CD27+ T-lymphocyte values at 3, 6, 9, 12months post-HSCT were recorded: for ECP patients, values were recorded at 3, 6, 9, 12months during ECP. Differences were compared using the Kruskal-Wallis test. 41 patients had no aGVHD, 23 had aGVHD treated topically or systemically (25), 13 received ECP. Rate of thymopoiesis was significantly different between all groups at all time-points post-transplant (p=0.002, p<0.001, p<0.001, p=0.001 respectively). Even mild aGVHD impairs thymopoiesis. Worst recovery was in ECP patients. Earlier institution of ECP may speed thymic recovery.

The health economic burden that acute and chronic wounds impose on an average clinical commissioning group/health board in the UK.

OBJECTIVE: To estimate the patterns of care and related resource use attributable to managing acute and chronic wounds among a catchment population of a typical clinical commissioning group (CCG)/health board and corresponding National Health Service (NHS) costs in the UK. METHOD: This was a sub-analysis of a retrospective cohort analysis of the records of 2000 patients in The Health Improvement Network (THIN) database. Patients' characteristics, wound-related health outcomes and health-care resource use were quantified for an average CCG/health board with a catchment population of 250,000 adults ≥18 years of age, and the corresponding NHS cost of patient management was estimated at 2013/2014 prices. RESULTS: An average CCG/health board was estimated to be managing 11,200 wounds in 2012/2013. Of these, 40% were considered to be acute wounds, 48% chronic and 12% lacking any specific diagnosis. The prevalence of acute, chronic and unspecified wounds was estimated to be growing at the rate of 9%, 12% and 13% per annum respectively. Our analysis indicated that the current rate of wound healing must increase by an average of at least 1% per annum across all wound types in order to slow down the increasing prevalence. Otherwise, an average CCG/health board is predicted to manage ~23,200 wounds per annum by 2019/2020 and is predicted to spend a discounted (the process of determining the present value of a payment that is to be received in the future) £50 million on managing these wounds and associated comorbidities. CONCLUSION: Real-world evidence highlights the substantial burden that acute and chronic wounds impose on an average CCG/health board. Strategies are required to improve the accuracy of diagnosis and healing rates.

Clinical outcomes and cost-effectiveness of three different compression systems in newly-diagnosed venous leg ulcers in the UK.

OBJECTIVE: To assess clinical outcomes and cost-effectiveness of using a two-layer cohesive compression bandage (TLCCB; Coban 2) compared with a two-layer compression system (TLCS; KTwo) and a four-layer compression system (FLCS; Profore) in treating newly-diagnosed venous leg ulcers (VLUs) in clinical practice in the UK, from the perspective of the NHS. METHOD: This was a retrospective cohort analysis of the case records of patients with newly-diagnosed VLUs randomly extracted from The Health Improvement Network (THIN) database (a nationally representative database of clinical practice among patients registered with general practitioners in the UK) who were treated with either TLCCB (n=200), TLCS (n=200) or FLCS (n=200). The clinical outcomes and cost-effectiveness of the alternative compression systems were estimated over six months after starting treatment. RESULTS: Patients' mean age was 72 years and 58% were female. Time from wound onset to the start of compression was a mean of two months, and when starting compression the wound size was a mean of 45 cm2. The distribution of healing was significantly different between the three groups; 76% of wounds in the TLCCB group healed by six months compared with 70% and 64% in the TLCS and FLCS groups, respectively (p=0.006). Time to healing was significantly less in the TLCCB group compared with the two other groups (p=0.003). Patients in the TLCCB group experienced better health-related quality of life over six months (0.413 quality-adjusted life years (QALYs) per patient), compared with the TLCS and FLCS groups (0.404 and 0.396 QALYs per patient, respectively). The mean six-month NHS management cost was £3045, £3842 and £4480 per patient in the TLCCB, TLCS and FLCS groups, respectively. CONCLUSION: Real-world evidence demonstrates that treating newly-diagnosed VLUs with TLCCB, compared with the other two compression systems, affords a more cost-effective use of NHS-funded resources in clinical practice since it resulted in an increased healing rate, better health-related quality of life and a reduction in NHS management cost.

Cost-effectiveness of using adjunctive porcine small intestine submucosa tri-layer matrix compared with standard care in managing diabetic foot ulcers in the US.

OBJECTIVE: To estimate the cost-effectiveness of using tri-layer porcine small intestine submucosa (SIS; Oasis Ultra) as an adjunct to standard care compared with standard care alone in managing diabetic foot ulcers (DFUs) in the US, from the perspective of Medicare. METHOD: A Markov model was constructed to simulate the management of diabetic neuropathic lower extremity ulcers over a period of one year in the US. The model was used to estimate the cost-effectiveness of initially using adjunctive SIS compared with standard care alone to treat a DFU in the US at 2016 prices. RESULTS: At 12 months after the start of treatment, the use of adjunctive SIS instead of standard care alone is expected to lead to a 42 % increase in the number of ulcer-free months, 32 % increase in the probability of healing, a 3 % decrease in the probability of developing complicated ulcers and a 1 % decrease in the probability of undergoing an amputation. Health-care resource use is expected to be reduced by 11-14 % among patients who are initially managed with adjunctive SIS compared with those initially managed with standard care alone, with the exception of debridement, which is expected to be reduced by 35 %. Hence, the total health-care cost of starting treatment with adjunctive SIS instead of standard care alone was estimated to reduce payer costs by 1% (i.e. $105 per patient) over 12 months following the start of treatment. CONCLUSION: Within the study's limitations, the use of adjunctive SIS instead of standard care alone improves outcome for less cost and thereby affords a cost-effective use of Medicare-funded resources in the management of neuropathic foot ulcers among adult patients with type 1 or 2 diabetes mellitus in the US.

Challenges for defining minimal clinically important difference (MCID) after spinal cord injury.

STUDY DESIGN: This is a review article. OBJECTIVES: This study discusses the following: (1) concepts and constraints for the determination of minimal clinically important difference (MCID), (2) the contrasts between MCID and minimal detectable difference (MDD), (3) MCID within the different domains of International Classification of Functioning, disability and health, (4) the roles of clinical investigators and clinical participants in defining MCID and (5) the implementation of MCID in acute versus chronic spinal cord injury (SCI) studies. METHODS: The methods include narrative reviews of SCI outcomes, a 2-day meeting of the authors and statistical methods of analysis representing MDD. RESULTS: The data from SCI study outcomes are dependent on many elements, including the following: the level and severity of SCI, the heterogeneity within each study cohort, the therapeutic target, the nature of the therapy, any confounding influences or comorbidities, the assessment times relative to the date of injury, the outcome measurement instrument and the clinical end-point threshold used to determine a treatment effect. Even if statistically significant differences can be established, this finding does not guarantee that the experimental therapeutic provides a person living with SCI an improved capacity for functional independence and/or an increased quality of life. The MDD statistical concept describes the smallest real change in the specified outcome, beyond measurement error, and it should not be confused with the minimum threshold for demonstrating a clinical benefit or MCID. Unfortunately, MCID and MDD are not uncomplicated estimations; nevertheless, any MCID should exceed the expected MDD plus any probable spontaneous recovery. CONCLUSION: Estimation of an MCID for SCI remains elusive. In the interim, if the target of a therapeutic is the injured spinal cord, it is most desirable that any improvement in neurological status be correlated with a functional (meaningful) benefit.

Clinical outcomes and cost-effectiveness of an externally applied electroceutical device in managing venous leg ulcers in clinical practice in the UK.

OBJECTIVE: To estimate the cost-effectiveness of treating patients with a venous leg ulcer (VLU) with an externally applied electroceutical (EAE) device, plus dressings and compression bandaging or continuing with their previous care plan, from the perspective of the National Health Service (NHS) in the UK. METHOD: This was a prospective, single-arm, non-blinded, clinical and economic evaluation of EAE therapy performed in 2013/14. Patients' VLUs were treated with six active units of EAE therapy (each unit for two days) plus dressings and compression bandaging over a period of 12 days. Afterwards, patients were managed with a combination of dressings and bandages. Each patient acted as their own control so that clinical outcomes, resource use and costs associated with the wound over 12 months before the start of EAE therapy were retrospectively compared with the first 12 months after the start of treatment. The relative cost-effectiveness of EAE therapy was estimated at 2013/14 prices. RESULTS: Within 12 months of starting EAE therapy 77% of all wounds healed and the other 23% improved. This difference in effectiveness between the 12-months period before and after EAE therapy was estimated to yield a 12% improvement in health gain of 0.09 QALYs (p<0.01), a 34% reduction in the requirement for nurse visits (from a mean 50.7 to 33.3 visits per patient) and a 26% reduction in the number of dressings. This resulted in an 11% reduction in the NHS cost of VLU management over 12 months after the start of treatment when compared with the previous 12 months (from £1,981 to £1,754 per patient). Hence, use of EAE therapy was found to be a dominant treatment (i.e. improved outcome for less cost). CONCLUSION: Within the study's limitations, use of the EAE device potentially affords the NHS a cost-effective treatment for managing VLUs when compared with patients remaining on their previous care plan.

Clinical outcomes and cost-effectiveness of three alternative compression systems used in the management of venous leg ulcers.

OBJECTIVE: To assess clinical outcomes and cost-effectiveness of using a two-layer cohesive compression bandage (TLCCB; Coban 2) compared with a two-layer compression system (TLCS; Ktwo) and a four-layer compression system (FLCS; Profore) in treating venous leg ulcers (VLUs) in clinical practice in the UK, from the perspective of the National Health Service (NHS). METHOD: This was a retrospective analysis of the case records of VLU patients, randomly extracted from The Health Improvement Network (THIN) database (a nationally representative database of clinical practice among patients registered with general practitioners in the UK), who were treated with either TLCCB (n=250), TLCS (n=250) or FLCS (n=175). Clinical outcomes and health-care resource use (and costs) over six months after starting treatment with each compression system were estimated. Differences in outcomes and resource use between treatments were adjusted for differences in baseline covariates. RESULTS: Patients' mean age was 75 years old and 57% were female. The mean time with a VLU was 6-7 months and the mean initial wound size was 77-85 cm2. The overall VLU healing rate, irrespective of bandage type, was 44% over the six months' study period. In the TLCCB group, 51% of wounds had healed by six months compared with 40% (p=0.03) and 28% (p=0.001) in the TLCS and FLCS groups, respectively. The mean time to healing was 2.5 months. Patients in the TLCCB group experienced better health-related quality of life (HRQoL) over six months (0.374 quality-adjusted life years (QALYs) per patient), compared with the TLCS (0.368 QALYs per patient) and FLCS (0.353 QALYs per patient). The mean six-monthly NHS management cost was £2,413, £2,707 and £2,648 per patient in the TLCCB, TLCS and FLCS groups, respectively. CONCLUSION: Despite the systems studied reporting similar compression levels when tested in controlled studies, real-world evidence demonstrates that initiating treatment with TLCCB, compared with the other two compression systems, affords a more cost-effective use of NHS-funded resources in clinical practice, since it resulted in an increased healing rate, better HRQoL and a reduction in NHS management cost. The evidence also highlighted the lack of continuity between clinicians managing a wound, the inconsistent nature of the administered treatments and the lack of specialist involvement, all of which may impact on healing. DECLARATION OF INTEREST: This study was supported by an unrestricted research grant from 3M Health Care, UK. 3M Health Care had no influence on the study design, the collection, analysis, and interpretation of data, or on the writing of, and decision to submit for publication, the manuscript.

Comparison of colorectal cancer screening and diagnoses in HIV-positive and HIV-negative veterans.

Non-AIDS defining malignancies, including colorectal cancer (CRC), are emerging as significant problems in HIV-infected people. Some data suggest that HIV-positive patients have higher incidence of CRC at younger ages than those who are HIV-negative. This investigation examined CRC rates and screening types and trends between 943 HIV-infected cases and their age, race, and gender matched HIV-negative controls (n = 943) from 1 January 2005 to 31 December 2008 at the Atlanta VA Medical Center. The most common screening type among these patients was fecal occult blood testing (FOBT), but colonoscopies were more common in the controls (16.4% for cases, 27.5% for controls; p < 0.0001). Almost half of all patients included in this analysis did not have any screening for CRC during the four years of follow-up even though average age was 55 years. Fifty-one percent of cases had at least one screening test during follow-up compared to 48% of the controls; 7.6% of the cases had a screening each of the four years compared to only 2.4% of the controls (p < 0.0001). Ten HIV-positive patients were diagnosed with CRC during the study period compared to no CRC diagnoses among controls (p = 0.0015), though there was no difference in the diagnosis of colon polyps (4.6% vs. 5.1%, p = 0.5911). These data also suggest a discrepancy in CRC incidence between race and age groups: 80% of HIV-positive cases diagnosed with CRC during the study were black and two were less than 50 years of age. Future studies will need to address whether different recommendations are needed for screening based on HIV status, younger age, or race.

Costs and outcomes over 36 years of patients with phenylketonuria who do and do not remain on a phenylalanine-restricted diet.

BACKGROUND: To quantify the costs and consequences of managing phenylketonuria (PKU) in the UK and to estimate the potential implications to the UK's National Health Service (NHS) of keeping patients on a phenylalanine-restricted diet for life. METHOD: A computer-based model was constructed depicting the management of PKU patients over the first 36 years of their life, derived from patients suffering from this metabolic disorder in The Health Improvement Network database (a nationally representative database of patients registered with general practitioners in the UK). The model was used to estimate the incidence of co-morbidities and the levels of healthcare resource use and corresponding costs over the 36 years. RESULTS: Patients who remained on a phenylalanine-restricted diet accounted for 38% of the cohort. Forty-seven per cent of patients discontinued their phenylalanine-restricted diet between 15 and 25 years of age. Of these, 73% remained off diet and 27% restarted a restricted diet at a mean 30 years of age. Fifteen per cent of the cohort had untreated PKU. Eleven per cent of patients who remained on a phenylalanine-restricted diet for 36 years received the optimum amount of prescribed amino acid supplements. Patients had a mean 12 general practitioner visits per year and one hospital outpatient visit annually, but phenylalanine levels were only measured once every 18 to 24 months. The mean NHS cost (at 2007/08 prices) of managing a PKU sufferer over the first 36 years of their life was estimated to range between £21 000 and £149 000, depending on the amount of prescribed nutrition they received. CONCLUSION: The findings suggest that the majority of patients with PKU were under-treated. The NHS cost of patient management should not be an obstacle to encouraging patients to remain on a restricted diet until further information becomes available about the long-term clinical impact of stopping such a diet. Nevertheless, patients require counselling and managed follow up regardless of the choices they make about their diet.

Clinical and cost-effectiveness of absorbent dressings in the treatment of highly exuding VLUs.

OBJECTIVE: To estimate the clinical effectiveness and cost effectiveness of using a sodium carboxymethylcellulose dressing (CMC [Aquacel]) and four super absorbent dressings (DryMax Extra[DM], Flivasorb [F], Kerramax [K] and sachet S [S]) in the treatment of highly exuding chronic venous leg ulcers (VLUs) in the UK, from the perspective of the National Health Service (NHS). METHOD: A decision model was constructed depicting the patient pathways and associated management of a cohort of 439 patients with highly exuding chronic VLUs of;;: 3 months of age. The model was based on the case records of a cohort of matched patients from The Health Improvement Network (THIN)database (a nationally representative database of patients registered with general practitioners (GPs) in the UK) who were treated with one of the five dressings. The model estimated the costs and outcomes of patient management over 6 months and the relative cost-effectiveness of using each dressing. RESULTS: Patients' mean age was 73.1 years, and 46% were female. Between 39% and 56% ofVLUs healed by 6 months. CMC-treated wounds that remained unhealed increased in size by 43% over the study period, whereas unhealed wounds treated with the other dressings decreased in size by a mean 34%. Consequently, CMC was excluded from the cost-effectiveness analysis. The 6-monthly NHS cost of managing a VLU with S was £3700 per patient, which was 15-28% lower than the cost of managing patients with the other three super absorbents. Additionally, use of S improved patients' health status to a greater extent than the other three super absorbents, since S-treated patients accrued 0.3-3% more QALYs. Starting treatment with S was the preferred strategy followed by DM, K and Fin that order. CONCLUSION: Within the limitations of the data set,S affords the NHS a cost-effective treatment for managing highly exuding chronic VLUs of ≥3 months of age, compared with DM, F, K and CMC.

Is it time to re-appraise the role of compression in non-healing venous leg ulcers?

OBJECTIVE: To evaluate the role of compression in non-healing venous leg ulcers (VLUs) of > 3 months' duration. METHOD: Patients' records from three independent data sets of non-healing VLUs of > 3 months'duration were re-analysed.Two data sets were separate audits of clinical practice and the third comprised patients' records from a randomised controlled trial. Some patients in each data set were never treated with compression. The effect of compression on healing at 6 months was tested with logistic regression. RESULTS: In each data set, patients in the compression and no-compression groups were matched according to ulcer size and duration; there were no differences in comorbidities. Comparing the no-compression with the compression groups, the healing rate at 6 months was 68% vs 48% in study 1, 12% vs 6% in study 2, and 26% vs 11% in study 3. Use of compression was found to be an independent predictor of not healing with an odds ratio of 0.422, 0.456 and 0.408 in studies 1, 2 and 3 respectively. CONCLUSION: The healing rate of non-healing VLUs of > 3 months' duration in the no-compression groups was double that of VLUs in the compression groups. These findings have the potential for treatment modification if confirmed in a prospective trial. DECLARATION OF INTEREST: There were no external sources of funding for this study. The authors have no conflicts of interest that are directly relevant to the content of this manuscript, which remains their sole responsibility.

Conduction of topologically protected charged ferroelectric domain walls.

We report on the observation of nanoscale conduction at ferroelectric domain walls in hexagonal HoMnO(3) protected by the topology of multiferroic vortices using in situ conductive atomic force microscopy, piezoresponse force microscopy, and Kelvin-probe force microscopy at low temperatures. In addition to previously observed Schottky-like rectification at low bias [Phys. Rev. Lett. 104, 217601 (2010)], conductance spectra reveal that negatively charged tail-to-tail walls exhibit enhanced conduction at high forward bias, while positively charged head-to-head walls exhibit suppressed conduction at high reverse bias. Our results pave the way for understanding the semiconducting properties of the domains and domain walls in small-gap ferroelectrics.

Relative cost-effectiveness of a skin protectant in managing venous leg ulcers in the UK.

OBJECTIVE: To estimate the clinical and cost-effectiveness of using a skin protectant (Cavilon No Sting Barrier Film [NSBF] or Cavilon Durable Barrier Cream [DBC]; 3M) compared with not using a skin protectant in the management of venous leg ulcers (VLUs), in the UK. METHOD: A decision model was constructed depicting the patient pathways and associated management of a cohort of patients with and without a Cavilon formulation, plus dressings and compression. The model was based on the case records of a cohort of matched patients from The Health Improvement Network (THIN) database, who were first diagnosed with a VLU between 1 Jan 2008 and 31 Dec 2009. The model estimated the costs and outcomes of patient management over 6 months and the cost-effectiveness of using a Cavilon formulation relative to not using a skin protectant. RESULTS: Patients' mean age was 80.2 years and 61% were female. Sixty-five per cent (n=166) of Cavilon patients received NSBF, and 35% received DBC. Between 6% and 9% of VLUs were healed at 6 months and 53-66% became infected. Healing was affected by a patient's age (OR: 0.944 for each additional year), but not by gender, level of exudate or wound size. There was a significantly greater reduction in wound size among patients in the NSBF group than in the other two groups (p<0.001). Additionally, there was no significant difference in the initial wound size of those VLUs that did and did not heal in the two Cavilon groups; however, initial size of the VLUs that healed in the control group was significantly smaller than those that did not (p<0.001). Resource use was similar between the three groups. Patients were predominantly managed by practice nurses, with a mean 37-38 nurse visits over the study period. Patients' dressings were changed, on average, every 4-5 days, with a mean of 3 dressings under a compression bandage. The total 6-monthly NHS cost of managing a VLU was ~£2200. Practice nurse visits were the primary cost driver, accounting for up to 58% of the 6-monthly NHS cost, whereas dressings accounted for <10% of the cost. CONCLUSION: Use of NSBF leads to significantly greater wound size reduction than that observed in the other two groups and may facilitate the healing of larger wounds without increasing costs. Hence, use of NSBF for peri-wound skin protection in patients with exuding VLUs is the preferred treatment strategy. DECLARATION OF INTEREST: This study was sponsored by 3M Health Care, manufacturers of Cavillon NSBF and Cavillon DBC. However, the authors have no other conflicts of interest that are directly relevant to the content of this manuscript, which remains their sole responsibility.

Evaluation of the impact of direct plating, broth enrichment, and specimen source on recovery and diversity of methicillin-resistant Staphylococcus aureus isolates among HIV-infected outpatients.

We compared recovery of Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) from nasal and groin swab specimens of 600 HIV-infected outpatients by selective and nonselective direct plating and broth enrichment. Swabs were collected at baseline, 6-month, and 12-month visits and cultured by direct plating to mannitol salt agar (MSA) and CHROMagar MRSA (CM) and overnight broth enrichment with subculture to MSA (broth). MRSA isolates were characterized by pulsed-field gel electrophoresis (PFGE), staphylococcal cassette chromosome mec (SCCmec) typing, and PCR for the Panton-Valentine leukocidin. At each visit, 13 to 15% of patients were colonized with MRSA and 30 to 33% were colonized with methicillin-susceptible S. aureus (MSSA). Broth, CM, and MSA detected 95%, 82%, and 76% of MRSA-positive specimens, respectively. MRSA recovery was significantly higher from broth than CM (P ≤ 0.001) or MSA (P ≤ 0.001); there was no significant difference in recovery between MSA and CM. MSSA recovery also increased significantly when using broth than when using MSA (P ≤ 0.001). Among specimens collected from the groin, broth, CM, and MSA detected 88%, 54%, and 49% of the MRSA-positive isolates, respectively. Broth enrichment had a greater impact on recovery of MRSA from the groin than from the nose compared to both CM (P ≤ 0.001) and MSA (P ≤ 0.001). Overall, 19% of MRSA-colonized patients would have been missed with nasal swab specimen culture only. USA500/Iberian and USA300 were the most common MRSA strains recovered, and USA300 was more likely than other strain types to be recovered from the groin than from the nose (P = 0.05).

Methicillin-resistant Staphylococcus aureus colonization in HIV-infected outpatients is common and detection is enhanced by groin culture.

SUMMARYAlthough high rates of clinical infection with methicillin-resistant Staphylococcus aureus (MRSA) have been reported in HIV-infected adults, data on MRSA colonization are limited. We enrolled HIV-infected adults receiving care at the Atlanta VA Medical Center. Swabs from each participant's nares and groin were cultured with broth enrichment for S. aureus. Of 600 HIV-infected adults, 79 (13%) were colonized with MRSA and 180 (30%) with methicillin-susceptible S. aureus. MRSA pulsed-field gel electrophoresis types USA300 (n=44, 54%) and USA500/Iberian (n=29, 35%) predominated. Inclusion of groin swabs increased MRSA detection by 24% and USA300 detection by 38%. In multivariate analysis, MRSA colonization compared to no MRSA colonization was associated with a history of MRSA clinical infection, rarely or never using condoms, and contact with prisons and jails. In summary, the prevalence of MRSA colonization was high in this study of HIV-infected adults and detection of USA300 was enhanced by groin culture.

Characterization of neurological recovery following traumatic sensorimotor complete thoracic spinal cord injury.

STUDY DESIGN: Retrospective, longitudinal analysis of sensory, motor and functional outcomes from individuals with thoracic (T2-T12) sensorimotor complete spinal cord injury (SCI). OBJECTIVES: To characterize neurological changes over the first year after traumatic thoracic sensorimotor complete SCI. METHODS: A dataset of 399 thoracic complete SCI subjects from the European Multi-center study about SCI (EMSCI) was examined for neurological level, sensory levels and sensory scores (pin-prick and light touch), lower extremity motor score (LEMS), ASIA Impairment Scale (AIS) grade, and Spinal Cord Independence Measure (SCIM) over the first year after SCI. RESULTS: AIS grade conversions were limited. Sensory scores exhibited minimal mean change, but high variability in both rostral and caudal directions. Pin-prick and light touch sensory levels, as well as neurological level, exhibited minor changes (improvement or deterioration), but most subjects remained within one segment of their initial injury level after 1 year. Recovery of LEMS occurred predominantly in subjects with low thoracic SCI. The sensory zone of partial preservation (ZPP) had no prognostic value for subsequent recovery of sensory levels or LEMS. However, after mid or low thoracic SCI, ≥3 segments of sensory ZPP correlated with an increased likelihood for AIS grade conversion. CONCLUSION: The data suggest that a sustained deterioration of three or more thoracic sensory levels or loss of upper extremity motor function are rare events and may be useful for tracking the safety of a therapeutic intervention in early phase acute SCI clinical trials, if a significant proportion of study subjects exhibit such an ascent.

Extent of spontaneous motor recovery after traumatic cervical sensorimotor complete spinal cord injury.

STUDY DESIGN: Retrospective, longitudinal analysis of motor recovery data from individuals with cervical (C4-C7) sensorimotor complete spinal cord injury (SCI) according to the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI). OBJECTIVES: To analyze the extent and patterns of spontaneous motor recovery over the first year after traumatic cervical sensorimotor complete SCI. METHODS: Datasets from the European multicenter study about SCI (EMSCI) and the Sygen randomized clinical trial were examined for conversion of American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade, change in upper extremity motor score (UEMS) or motor level, as well as relationships between these measures. RESULTS: There were no overall differences between the EMSCI and Sygen datasets in motor recovery patterns. After 1 year, up to 70% of subjects spontaneously recovered at least one motor level, but only 30% recovered two or more motor levels, with lesser values at intermediate time points. AIS grade conversion did not significantly influence motor level changes. At 1 year, the average spontaneous improvement in bilateral UEMS was 10-11 motor points. There was only moderate relationship between a change in UEMS and a change in cervical motor level (r(2)=0.30, P<0.05). Regardless of initial cervical motor level, most individuals recover a similar number of motor points or motor levels. CONCLUSION: Careful tracking of cervical motor recovery outcomes may provide the necessary sensitivity and accuracy to reliably detect a subtle, but meaningful treatment effect after sensorimotor complete cervical SCI. The distribution of the UEMS change may be more important functionally than the total UEMS recovered.

Clinical outcomes and health-related quality of life (HRQOL) following haemopoietic stem cell transplantation (HSCT) for paediatric leukaemia.

BACKGROUND: Haemopoietic stem cell transplantation (HSCT) is a life-saving but intensive procedure associated with potentially severe adverse late effects. We aimed to determine morbidity and health-related quality of life (HRQOL) in a sample of survivors aged 8-18 years at least 1 year post HSCT for paediatric acute leukaemia, compared with a non-transplanted group of survivors matched for age, gender, initial disease and time since treatment. METHODS: Families (N = 54; HSCT n= 29) recruited from four UK centres completed measures of child behaviour and school attendance, HRQOL and finances. Mothers completed measures of their own well-being. Clinical outcome data were extracted from medical records. RESULTS: Children in the HSCT group had significantly more late effects and had received more tests for vision, bone, dental and skin health, and thyroid, lung, and gonadal function than the non-transplanted group. HRQOL scores for the HSCT group were significantly lower in all domains compared with the non-transplanted group and population norms, but were not significantly related to clinical indices. Mothers in the HSCT group had significantly poorer mental well-being than population norms. CONCLUSION: Significant morbidity and compromised HRQOL was found in survivors of HSCT. The burden of caring for a child after HSCT has a continuing toll on mothers' well-being.The importance of counselling families about possible long-term consequences is emphasized.

Modelling the cost-effectiveness of electric stimulation therapy in non-healing venous leg ulcers.

OBJECTIVE: To estimate the cost-effectiveness of using electric stimulation (ES) therapy (Accel-Heal) plus dressings and compression bandaging compared with dressings and compression bandaging alone in treating chronic, non-healing venous leg ulcers (VLUs) of >6 months' duration from the perspective of the National Health Service (NHS) in the UK. METHOD: A 5-month Markov model was constructed, depicting the management of a chronic, non-healing VLU of >6 months' duration. The model considers the decision by a clinician to continue with a patient's previous care plan (comprising dressings and compression bandaging) or treating with ES therapy plus dressings and compression bandaging. The model was used to estimate the relative cost-effectiveness of ES therapy at 2008-2009 prices. RESULTS: According to the model, 38% of VLUs are expected to heal within 5 months after starting ES therapy, with a further 57% expected to improve. This improvement in clinical outcome is expected to lead to a 6% health gain of 0.017 QALYs (from 0.299 to 0.316 QALYs) over 5 months. The model also showed that using ES therapy instead of continuing with a patient's previous care plan is expected to reduce the NHS cost of managing them by 15%, from £880 to £749, due in part to a 27% reduction in the requirement for nurse visits (from mean 49.0 to 35.9 visits per patient) over the first 5 months after the start of treatment. Hence, use of ES therapy was found to be a dominant treatment (improved outcome for less cost). CONCLUSION: Within the model's limitations, use of ES therapy potentially affords the NHS a cost-effective treatment, compared with patients remaining on their previous care plan in managing chronic, non-healing VLUs of >6 months' duration. However, this is dependant on the number of ES therapy units per treatment, the unit cost of the device, and the number of nurse visits required to manage patients in clinical practice. DECLARATION OF INTEREST: This study was sponsored by Synapse Microcurrent Ltd., manufacturers of Accel-Heal. The authors have no other conflicts of interest that are directly relevant to the content of this manuscript. In particular, Synapse Microcurrent Ltd. had no role in the study design, in the collection, analysis and interpretation of data, or in writing the manuscript.

Clinical and economic evidence supporting a transparent barrier film dressing in incontinence-associated dermatitis and peri-wound skin protection.

OBJECTIVE: To summarise the clinical and economic literature relating to the effect of Cavilon No Sting Barrier Film on the incidence of incontinence-associated dermatitis, which is a risk factor for pressure ulceration and exudate-related peri-wound skin damage. METHOD: A systematic literature search was performed using available computerised databases for publications on Cavilon barrier film and other relevant terms. Six clinical studies were identified providing data on 1,563 patients treated with the barrier film or a comparator. The publications comprised prospective studies, randomised and non-randomised studies, multicentre trials, single-centre reports and a volunteer study. Due to the nature of the comparators, five studies were open-label. Differences in methodology and outcomes made a qualitative review the most appropriate analysis. RESULTS: The barrier film was at least as effective as petroleum ointments and more effective than zinc oxide formulations in preventing incontinence-associated dermatitis. The barrier film was also effective in peri-wound skin protection, although its clinical efficacy was not significantly different to that of petroleum ointments and zinc oxide formulations. Nevertheless, the barrier film was more cost-effective than either petroleum ointments or zinc oxide formulations in managing incontinence-associated dermatitis and peri-wound skin protection, largely due to savings in nursing time. CONCLUSION: The barrier film is at least as clinically effective and potentially more cost-effective in incontinence-associated dermatitis prophylaxis and peri-wound skin protection than petroleum ointments or zinc oxide formulations, releasing health care resources for alternative use. Further studies are required to quantify the relative efficacy and cost-effectiveness of the barrier film and other barrier formulations in different clinical settings and enhance the quality of the evidence base.