Priority recommendations for the implementation of patient-reported outcomes in clinical cancer care: a Delphi study.

PURPOSE: The aim of this study was to develop priority recommendations for the service level implementation of patient-reported outcomes (PROs) into clinical cancer care. METHODS: Development of draft guidance statements was informed by a literature review, the Knowledge to Action (KTA) implementation framework, and discussion with PRO experts and cancer survivors. A two-round modified Delphi survey with key stakeholders including cancer survivors, clinical and research experts, and Information Technology specialists was undertaken. Round 1 rated the importance of the statements and round 2 ranked statements in order of priority. RESULTS: Round 1 was completed by 70 participants with round 2 completed by 45 participants. Forty-seven statements were rated in round 2. In round 1, the highest agreement items (>90% agreement) included those that focused on the formation of strong stakeholder partnerships, ensuring ongoing communication within these partnerships, and the use of PROs for improvement and guidance in clinical care. Items ranked as the highest priorities in round 2 included assessment of current staff capabilities and service requirements, mapping of workflows and processes to enable collection, and using collected PROs to guide improved health outcomes. CONCLUSIONS: This stakeholder consultation process has identified key priorities in PRO implementation into clinical cancer care that include clinical relevance, stakeholder engagement, communication, and integration within the existing processes and capabilities. IMPLICATION FOR CANCER SURVIVORS: Routine adoption of PRO collection by clinical cancer services requires multiple implementation steps; of highest priority is strong engagement and communication with key stakeholders including cancer survivors.

Comparing complex perspectives on obesity drivers: action-driven communities and evidence-oriented experts.

INTRODUCTION: The Foresight obesity map represents an expert-developed systems map describing the complex drivers of obesity. Recently, community-led causal loop diagrams have been developed to support community-based obesity prevention interventions. This paper presents a quantitative comparison between the Foresight obesity systems map and a community-developed map of the drivers of obesity. METHODS: Variables from a community-developed map were coded against the thematic clusters defined in the Foresight map to allow comparison of their sizes and strength of adjoining causal relationships. Central variables were identified using techniques from network analysis. These properties were compared to understand the similarities and differences between the systems as defined by the two groups. RESULTS: The community map focused on environmental influences, such as built physical activity environment (18% of variables) and social psychology (38%). The Foresight map's largest cluster was physiology (23%), a minimal focus in the community map (2%). Network analysis highlighted media and available time within both maps, but variables related to school and sporting club environments were unique to the community map. CONCLUSION: Community stakeholders focus on modifiable social and environmental drivers of obesity. Capturing local perspectives is critical when using systems maps to guide community-based obesity prevention.

Sustaining obesity prevention in communities: a systematic narrative synthesis review.

Obesity is a global problem for which sustainable solutions are yet to be realized. Community-based interventions have improved obesity-related behaviours and obesity in the short term. Few papers have explored how to make the interventions and their intended outcomes sustainable. The aim of this paper is to identify factors that contribute to the sustainability of community-based obesity prevention interventions and their intended outcomes. A systematic narrative synthesis review was conducted of published community-based obesity prevention interventions to identify factors contributing to intervention sustainability. Data extracted were included study authors' perspectives of intervention success and sustainability. Eighty-one papers met the inclusion criteria, and from these we identified ten factors that contribute to sustainability: resourcing, leadership, workforce development, community engagement, partnerships, policy, communications, adaptability, evaluation and governance. This review of community-based obesity prevention interventions gives rise to optimism that sustainable change is possible. We propose a framework to help practitioners build sustainability into their interventions and report on them so that others can also benefit.

When ignorance is bliss: weight perception, body mass index and quality of life in adolescents.

BACKGROUND/OBJECTIVES: Body weight is negatively associated with adolescent Health-Related Quality of Life (HRQoL). Despite this well-established relationship, some adolescents with obesity do not display the expected HRQoL decreases. This study hypothesised weight perception as a moderator of the association between weight status and adolescent HRQoL. SUBJECTS/METHODS: Subjects were secondary school students from an obesity prevention project in the Barwon South-West region of Victoria, Australia, entitled It's Your Move (N=3040). Measures included standardised body mass index (BMI-z; World Health Organization growth standards), weight perception and HRQoL, measured by the Paediatric Quality of Life Inventory. Linear regression and average marginal effect analyses were conducted on cross-sectional baseline data to determine the significance of any interaction between weight perception and measured weight status in shaping adolescent HRQoL. RESULTS: The BMI-z/perceived weight status interaction was significantly associated with adolescent HRQoL outcomes. Adolescents with BMI z-scores in the overweight/obesity range who perceived themselves as overweight had lower HRQoL than those who perceived themselves as 'about right.' Conversely, adolescents with BMI scores in the lower end of the normal range or in the thinness range who perceived themselves as underweight had lower HRQoL than those with 'about right' perceptions. CONCLUSIONS: This was the first study to report third-variable impacts of a body-perception variable on the relationship between adolescent weight status and HRQoL. Adolescents' weight perceptions significantly moderated the relationship between overweight/obesity and reduced HRQoL. Adolescents who were outside the normal weight range and misperceived their objectively measured weight status enjoyed a higher HRQoL than adolescents whose weight perception was concordant with their actual weight status. These findings suggest that practitioners may need to exercise caution when educating adolescents about their weight status, as such 'reality checks' may negatively impact on adolescent HRQoL. It is suggested that more research be conducted to examine this potential effect.

Associations between obesogenic risk and depressive symptomatology in Australian adolescents: a cross-sectional study.

BACKGROUND: Depression and obesity are significant health concerns currently facing adolescents worldwide. This paper investigates the associations between obesity and related risk behaviours and depressive symptomatology in an Australian adolescent population. METHODS: Data from the Australian Capital Territory It's Your Move project, an Australian community-based intervention project were used. In 2012, 800 students (440 females, 360 males) aged 11-14 years (M=13.11 years, SD=0.62 years), from 6 secondary schools were weighed and measured and completed a questionnaire which included physical activity, sedentary behaviour and dietary intake. Weight status was defined by WHO criteria. A cut-off score ≥10 on the Short Mood and Feelings Questionnaire indicated symptomatic depression. Logistic regression was used to test associations. RESULTS: After controlling for potential confounders, results showed significantly higher odds of depressive symptomatology in males (OR=1.22, p<0.05) and females (OR=1.12, p<0.05) who exceeded guidelines for daily screen-time leisure sedentary activities. Higher odds of depressive symptoms were seen in females who consumed greater amounts of sweet drink (OR=1.18, p<0.05), compared to lower female consumers of sweet drinks, and males who were overweight/obese also had greater odds of depressive symptoms (OR=1.83, p<0.05) compared to male normal weight adolescents. CONCLUSIONS: This study demonstrates the associations between obesogenic risks and depression in adolescents. Further research should explore the direction of these associations and identify common determinants of obesity and depression. Mental health outcomes need to be included in the rationale and evaluation for diet and activity interventions.

Associations between obesogenic risk factors and depression among adolescents: a systematic review.

Adolescence is a transitional life phase that is associated with heightened risk for two major health conditions - obesity and mental health problems. Given the established comorbidity of obesity and depression, one avenue that warrants further exploration is the association between obesogenic risk and obesity in the expression and maintenance of depressive symptoms. The aim of the current systematic review was to identify and evaluate the empirical literature reporting the relationships between obesogenic risk factors (physical activity, sedentary behaviour, diet and weight status) and depression in adolescents. A search of five databases for studies published over the last decade found 24 studies eligible for review. Relationships were found between lack of physical exercise, heightened sedentary behaviour, poor diet quality, obese or overweight and depression in adolescence. However, the finding that obesogenic risk factors are associated with poor adolescent mental health should be interpreted with caution as data typically come from non-representative samples with less than optimal study design and methodology.

Large reductions in child overweight and obesity in intervention and comparison communities 3 years after a community project.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Childhood obesity has been increasing over decades and scalable, population-wide solutions are urgently needed to reverse this trend. Evidence is emerging that community-based approaches can reduce unhealthy weight gain in children. In some countries, such as Australia, the prevalence of childhood obesity appears to be flattening, suggesting that some population-wide changes may be underway. WHAT THIS STUDY ADDS: A community-based intervention project for obesity prevention in a rural town appears to have increasing effects 3 years after the end of the project, substantially reducing overweight and obesity by 6% points in new cohorts of children, 6 years after the original baseline. An apparent and unanticipated 'spillover' of effects into the surrounding region appeared to have occurred with 10%-point reductions in childhood overweight and obesity over the same time period. A 'viral-like' spread of obesity prevention efforts may be becoming possible and an increase in endogenous community activities appears to be surprisingly successful in reducing childhood obesity prevalence. BACKGROUND: The long-term evaluations of community-based childhood obesity prevention interventions are needed to determine their sustainability and scalability. OBJECTIVES: To measure the impacts of the successful Be Active Eat Well (BAEW) programme in Victoria, Australia (2003-2006), 3 years after the programme finished (2009). METHODS: A serial cross-sectional study of children in six intervention and 10 comparison primary schools in 2003 (n = 1674, response rate 47%) and 2009 (n = 1281, response rate 37%). Height, weight, lunch box audits, self-reported behaviours and economic investment in obesity prevention were measured. RESULTS: Compared with 2003, the 2009 prevalence of overweight/obesity (World Health Organization criteria) was significantly lower (P < 0.001) in both intervention (39.2% vs. 32.8%) and comparison (39.6% vs. 29.1%) areas, as was the mean standardized body mass index (0.79 vs. 0.65, 0.77 vs. 0.57, respectively) with no significant differences between areas. Some behaviours improved and a few deteriorated with any group differences favouring the comparison area. In 2009, the investment in obesity prevention in intervention schools was about 30 000 Australian dollars (AUD) per school per year, less than half the amount during BAEW. By contrast, the comparison schools increased from a very low base to over 66 000 AUD per school per year in 2009. CONCLUSIONS: The 8%-point reduction in overweight/obesity in both areas over 6 years from baseline to 3 years post-intervention was substantial. While the benefits of BAEW increased in the intervention community in the long term, the surrounding communities appeared to have more than caught up in programme investments and health gains, suggesting a possible 'viral spread' of obesity prevention actions across the wider region.

Inconsistent associations between sweet drink intake and 2-year change in BMI among Victorian children and adolescents.

OBJECTIVE: The aim of this study was to examine whether baseline (T1) or 2-year change in sweet drink intake in children and adolescents was associated with age- and gender-standardized body mass index (BMIz) at time two (T2), 2 years later. METHODS: Data on 1465 children and adolescents from the comparison groups of two quasi-experimental intervention studies from Victoria, Australia were analysed. At two time points between 2003 and 2008 (mean interval: 2.2 years) height and weight were measured and sweet drink consumption (soft drink and fruit juice/cordial) was assessed. RESULTS: No association was observed between T1 sweet drink intake and BMIz at T2 among children or adolescents. Children from higher socioeconomic status families who reported an increased intake of sweet drinks at T2 compared with T1 had higher mean BMIz at T2 (ß: 0.13, P = 0.05). There was no evidence of a dose-response relationship between sweet drink intake and BMIz. In supplementary analyses, we observed that more frequent usual consumption of fruit juice/cordial was associated with a higher BMIz at T2 among children. CONCLUSION: This study showed limited evidence of an association between sweet drink intake and BMIz. However, the association is complex and may be confounded by both dietary and activity behaviours.

The relationship between childhood weight, dental caries and eating practices in children aged 4-8 years in Australia, 2004-2008.

OBJECTIVES: The association between overweight/obesity and dental caries in children is contentious with studies variously reporting positive or negative associations between the two conditions. Since 1995, Australia has experienced a rise in the prevalence of both conditions in its children. This study investigated the association between child weight, diet and dental problems in a nationally representative sample. METHOD: Data from 4149 children (51.5% male) participating in the Longitudinal Study of Australian Children (LSAC) were used. The LSAC is a longitudinal study collecting data from a large representative cohort of Australian children; data from the first three waves were included with children aged 4-5 years, 6-7 years, and 8-9 years. Multivariate cross-sectional and prospective analyses were conducted to determine the relationships between child weight, diet and dental problems. RESULTS: Overweight/obesity was associated with sweet drink consumption and dental problems associated with consumption of fatty foods and sweet drinks. Underweight was associated with dental problems cross-sectionally, but both underweight and overweight at age 6-7 years predicted dental problems at age 8-9 years. CONCLUSIONS: Dental caries and body weight are influenced by diet. Overweight children may be consuming less fatty food but appear to be consuming more sweet drinks than normal-weight children, which can lead to both increased weight and dental caries. Dietary interventions designed to reduce the development of dental caries may also reduce the development and maintenance of overweight.

A survey of Core Medical Trainees' opinions on the ePortfolio record of educational activities: beneficial and cost-effective?

OBJECTIVES: To evaluate Core Medical Trainees' (CMTs) opinions on the role of the ePortfolio in postgraduate education. DESIGN AND SETTING: Cross-sectional survey of 91 CMTs in five NHS trusts within the South Thames Deanery. PARTICIPANTS: Completed surveys were received from 80 Core Medical Trainees. RESULTS: A total of 84% agreed that an ongoing record of progress is necessary, only 5% felt the ePortfolio represents value for money; 78% of respondents were unclear as to how the Freedom of Information Act (2000) impacts on the ePortfolio, and most were uninformed of the extent to which their entries can be accessed by third parties. CONCLUSIONS: Trainees recognise the importance of recording ongoing progress, but most consider the ePortfolio to be poor value for money. There is uncertainty regarding ownership of information held on ePortfolio, and to what extent it can be accessed. There are inadequate opportunities to discuss concerns. This requires further deliberation and until things are clarified, trainees may not fully engage with the resource.

Experiences and challenges in implementing complex community-based research project: the Pacific Obesity Prevention in Communities project.

Policy makers throughout the world are struggling to find effective ways to prevent the rising trend of obesity globally, particularly among children. The Pacific Obesity Prevention in Communities project was the first large-scale, intervention research project conducted in the Pacific aiming to prevent obesity in adolescents. The project spanned four countries: Australia, New Zealand, Fiji and Tonga. This paper reports on the strengths and challenges experienced from this complex study implemented from 2004 to 2009 across eight cultural groups in different community settings. The key strengths of the project were its holistic collaborative approach, participatory processes and capacity building. The challenges inherent in such a large complex project were underestimated during the project's development. These related to the scale, complexity, duration, low research capacity in some sites and overall coordination across four different countries. Our experiences included the need for a longer lead-in time prior to intervention for training and up-skilling of staff in Fiji and Tonga, investment in overall coordination, data quality management across all sites and the need for realistic capacity building requirements for research staff. The enhanced research capacity and skills across all sites include the development and strengthening of research centres, knowledge translation and new obesity prevention projects.

The Pacific Obesity Prevention in Communities project: project overview and methods.

Obesity is increasing worldwide with the Pacific region having the highest prevalence among adults. The most common precursor of adult obesity is adolescent obesity making this a critical period for prevention. The Pacific Obesity Prevention in Communities project was a four-country project (Fiji, Tonga, New Zealand and Australia) designed to prevent adolescent obesity. This paper overviews the project and the methods common to the four countries. Each country implemented a community-based intervention programme promoting healthy eating, physical activity and healthy weight in adolescents. A community capacity-building approach was used, with common processes employed but with contextualized interventions within each country. Changes in anthropometric, behavioural and perception outcomes were evaluated at the individual level and school environments and community capacity at the settings level. The evaluation tools common to each are described. Additional analytical studies included economic, socio-cultural and policy studies. The project pioneered many areas of obesity prevention research: using multi-country collaboration to build research capacity; testing a capacity-building approach in ethnic groups with very high obesity prevalence; costing complex, long-term community intervention programmes; systematically studying the powerful socio-cultural influences on weight gain; and undertaking a participatory, national, priority-setting process for policy interventions using simulation modelling of cost-effectiveness of interventions.

Reduction in overweight and obesity from a 3-year community-based intervention in Australia: the 'It's Your Move!' project.

'It's Your Move!' was a 3-year intervention study implemented in secondary schools in Australia as part of the Pacific Obesity Prevention In Communities Project. This paper reports the outcome results of anthropometric indices and relevant obesity-related behaviours. The interventions focused on building the capacity of families, schools and communities to promote healthy eating and physical activity. Baseline response rates and follow-up rates were 53% and 69% respectively for the intervention group (n=5 schools) and 47% and 66% respectively for the comparison group (n=7 schools). Statistically significant relative reductions in the intervention versus comparison group were observed: weight (-0.74 kg, P < 0.04), and standardized body mass index (-0.07, P<0.03), and non-significant reductions in prevalence of overweight and obesity (0.75 odds ratio, P=0.12) and body mass index (-0.22, P=0.06). Obesity-related behavioural variables showed mixed results with no pattern of positive intervention outcomes. In conclusion, this is the first study to show that long-term, community-based interventions using a capacity-building approach can prevent unhealthy weight gain in adolescents. Obesity prevention efforts in this important transitional stage of life can be successful and these findings need to be translated to scale for a national effort to reverse the epidemic in children and adolescents.

Outcome results for the Ma'alahi Youth Project, a Tongan community-based obesity prevention programme for adolescents.

Tonga has a very high prevalence of obesity with steep increases during youth, making adolescence a critical time for obesity prevention. The Ma'alahi Youth Project, the Tongan arm of the Pacific Obesity Prevention in Communities project, was a 3-year, quasi-experimental study of community-based interventions among adolescents in three districts on Tonga's main island (Tongatapu) compared to the island of Vava'u. Interventions focused mainly on capacity building, social marketing, education and activities promoting physical activity and local fruit and vegetables. The evaluation used a longitudinal design (mean follow-up duration 2.4 years). Both intervention and comparison groups showed similar large increases in overweight and obesity prevalence (10.1% points, n = 815; 12.6% points, n = 897 respectively). Apart from a small relative decrease in percentage body fat in the intervention group (-1.5%, P < 0.0001), there were no differences in outcomes for any anthropometric variables between groups and behavioural changes did not follow a clear positive pattern. In conclusion, the Ma'alahi Youth Project had no impact on the large increase in prevalence of overweight and obesity among Tongan adolescents. Community-based interventions in such populations with high obesity prevalence may require more intensive or longer interventions, as well as specific strategies targeting the substantial socio-cultural barriers to achieving a healthy weight.

The effect of sporting events on emergency department attendance rates in a district general hospital in Northern Ireland.

BACKGROUND: Previous studies have reported a conflicting relationship between the effect of live and televised sporting events on attendance rates to emergency departments (ED). The objectives of this study were to investigate the relationship of major sporting events on emergency department attendance rates and to determine the potential effects of such events on service provision. METHODS: A retrospective analysis of ED attendances to a district general hospital (DGH) and subsequent admissions over a 24-h period following live and televised sporting activities was performed over a 5-year period. Data were compiled from the hospital's emergency record books including the number of attendances, patient demographics, clinical complaint and outcome. Review patients were excluded. Analysis of sporting events was compiled for live local, regional and national events as well as world-wide televised sporting broadcasts. RESULTS: A total of 137,668 (80,445 men) patients attended from April 2002 to July 2007. Mean attendance rate per day was 80 patients (men = 47). Mean admission rate was 13.6 patients per day. Major sporting events during the study period included; Soccer: 4 FA Cup and 1 World Cup (WC) finals; Rugby: 47 Six Nations, 25 Six nations games involving Ireland, 1 WC final, 2 WC semi-finals, 2 WC quarter-finals and 4 WC games involving Ireland; and Gaelic Football [Gaelic Athletic Association (GAA)]: 5 All-Ireland finals, 11 semi-finals, 11 quarter-finals and 5 provincial finals. There was a significantly higher patient admission rate during the soccer FA Cup final, Rugby Six Nations and games involving Ireland and for GAA semi- and quarter-final games (p = 0.001-0.01). There was no difference identified in total attendance or non-admission rates for sporting events throughout the study period. Although there was no correlation identified between any of these sporting events and total emergency department attendances (r < 0.15, p > 0.07), multinomial logistic regression demonstrated that FA Cup final (p = 0.001), Rugby Six Nations (p = 0.019), Rugby WC games involving Ireland (p = 0.003), GAA All-Ireland semi- and quarter-finals (p = 0.016; p = 0.016) were predictors of patient admission rates. CONCLUSION: This study suggests that live or televised sporting events do not significantly affect ED attendances to a DGH. However, some events appeared to be predictors of patient admission rates. Although it may be beneficial to consider the effect of sporting events on service stratification during these periods, the overall effect is probably minimal and should not create a major concern for future service provision despite the implementation of the European Working Time Directive.

Acetyl-l-carnitine and nucleoside reverse transcriptase inhibitor-associated neuropathy in HIV infection.

OBJECTIVES: Antiretroviral toxic neuropathy (ATN) is associated with dideoxynucleoside reverse transcriptase inhibitor use in patients infected with HIV, possibly as a result of mitochondrial toxicity. Acetyl-l-carnitine (ALC) has been linked to symptomatic improvement in ATN. We present an open-label single-arm pilot study to evaluate changes in intra-epidermal nerve fibre (IENF) density and mitochondrial DNA (mtDNA) copies/cell among subjects treated with 3000 mg ALC daily. METHODS: Punch skin biopsies were examined at baseline and after 24 weeks of therapy. Participants reported neuropathic symptoms using the Gracely Pain Intensity Score. Neurological examinations were completed. RESULTS: Twenty-one subjects completed the study. ALC was generally well tolerated. The IENF density did not change in cases completing 24 weeks of ALC therapy, with median (90% confidence interval) IENF changes of -1.70 (-3.50, infinity) (P=0.98) and 2.15 (-0.10, infinity) (P=0.11) for the distal leg and proximal thigh, respectively. Fat mtDNA copies/cell did not change with therapy. Improvements in neuropathic pain (P<0.01), paresthesias (P=0.01), and symptoms of numbness (P<0.01) were noted. Similarly, improvement was noted on the Gracely Pain Intensity Score. CONCLUSIONS: ALC therapy coincided with improvements in subjective measures of pain in this open-label single-arm study. However, changes were not observed in objective measures of IENF density or mtDNA levels, providing little objective support for use of ALC in this setting.

A multicenter trial of selegiline transdermal system for HIV-associated cognitive impairment.

BACKGROUND: Cognitive impairment continues to be a significant neurologic complication of HIV infection and has been associated with oxidative stress-induced neuronal injury. Selegiline is an MAO-B inhibitor with antioxidant and neurotrophic properties. This rationale has led to the design and implementation of this Selegiline Transdermal System (STS) study with the primary aims of assessing safety and tolerability of STS as well as improvement in cognitive performance. METHODS: HIV-1 infected individuals with impaired cognitive functioning were enrolled in this placebo-controlled, three-arm study of STS across 17 sites. Cognitive impairment was determined using a standard battery of neuropsychological tests. Subjects were randomized to receive STS 3 mg/24 hours, STS 6 mg/24 hours, or matching placebo patches daily. The primary efficacy endpoint was defined as the change in neuropsychological composite Z-score (NPZ-6) from baseline to week 24. Measures of safety included frequencies of adverse experiences and abnormal results on laboratory tests. RESULTS: A total of 128 subjects (88% men, 51% white) were enrolled, median age 45 years. Most subjects (62%) had mild to moderate AIDS dementia complex. The 24-week NPZ-6 median (interquartile range) changes were 0.22 (-0.28, 0.55) for the selegiline 3 mg/24 hours arm, 0.21 (-0.18, 0.62) for the selegiline 6 mg/24 hours arm, and 0.28 (-0.16, 0.64) for the placebo arm (a positive score indicates improvement from baseline) (p = 0.914). Severe laboratory abnormalities were few and occurred in similar proportion among the three treatment arms. CONCLUSION: Selegiline was safe and well tolerated by HIV-infected individuals with cognitive impairment and mild to moderate immune suppression; however, no cognitive or functional improvement was observed in this phase II study.

Correlates of epidermal nerve fiber densities in HIV-associated distal sensory polyneuropathy.

OBJECTIVE: To demonstrate the relationship between epidermal nerve fiber density (ENFD) in the leg and the phenotype of HIV-associated distal sensory polyneuropathy (HIV-DSP) in a multicenter prospective study (ACTG A5117). METHODS: A total of 101 HIV-infected adults, with CD4 cell count <300 cells/mm(3) and who had received antiretroviral therapy (ART) for at least 15 consecutive weeks, underwent standardized clinical and electrophysiologic assessment. All 101 subjects were biopsied at the distal leg (DL) and 99 at the proximal thigh (PT) at baseline. ENFD was assessed by skin biopsy using PGP9.5 immunostaining. Associations of ENFD with demographics, ART treatment, Total Neuropathy Score (TNS), sural sensory nerve action potential (SNAP) amplitude and conduction velocity, quantitative sensory testing (QST) measures, and neuropathic pain were explored. RESULTS: ENFD at the DL site correlated with neuropathy severity as gauged by TNS (p < 0.01), the level of neuropathic pain quantified by the Gracely Pain Scale (GPS) (p = 0.01) and Visual Analogue Scale (VAS) (p = 0.01), sural SNAP amplitude (p < 0.01), and toe cooling (p < 0.01) and vibration (p = 0.02) detection thresholds. ENFD did not correlate with neurotoxic ART exposure, CD4 cell count, or plasma HIV-1 viral load. CONCLUSIONS: In subjects with advanced HIV-1 infection, epidermal nerve fiber density (ENFD) assessment correlates with the clinical and electrophysiologic severity of distal sensory polyneuropathy (DSP). ENFD did not correlate with previously established risk factors for HIV-DSP, including CD4 cell count, plasma HIV-1 viral load, and neurotoxic antiretroviral therapy exposure.

HIV neuropathy natural history cohort study: assessment measures and risk factors.

BACKGROUND: Distal sensory polyneuropathy (DSP) is the most common neurologic complication of human immunodeficiency virus (HIV) infection. Risk factors for DSP have not been adequately defined in the era of highly active antiretroviral therapy. METHODS: The authors evaluated 101 subjects with advanced HIV infection over 48 weeks. Assessments included a brief peripheral neuropathy (PN) screen (BPNS), neurologic examination, nerve conduction studies, quantitative sensory testing (QST), and skin biopsies with quantitation of epidermal nerve fiber density. Data were summed into a Total Neuropathy Score (TNS). The presence, severity, and progression of DSP were related to clinical and laboratory results. RESULTS: The mean TNS (range 0 to 36) was 8.9, with 38% of subjects classified as PN-free, 10% classified as having asymptomatic DSP, and 52% classified as having symptomatic DSP. Progression in TNS from baseline to week 48 occurred only in the PN-free group at baseline (mean TNS change = 1.16 +/- 2.76, p = 0.03). Factors associated with progression in TNS were lower current TNS, distal epidermal denervation, and white race. As compared with the TNS diagnosis of PN at baseline, the BPNS had a sensitivity of 34.9% and a specificity of 89.5%. CONCLUSIONS: In this cohort of advanced human immunodeficiency virus (HIV)-infected subjects, distal sensory polyneuropathy was common and relatively stable over 48 weeks. Previously established risk factors, including CD4 cell count, plasma HIV RNA, and use of dideoxynucleoside antiretrovirals were not predictive of the progression of distal sensory polyneuropathy (DSP). Distal epidermal denervation was associated with worsening of DSP. As compared with the Total Neuropathy Score, the brief peripheral neuropathy screen had relatively low sensitivity and high specificity for the diagnosis of DSP.

Fetal membrane healing after spontaneous and iatrogenic membrane rupture: a review of current evidence.

In view of the important protective role of the fetal membranes, wound sealing, tissue regeneration, or wound healing could be life saving in cases of preterm premature rupture of the membranes. Although many investigators are studying the causes of preterm premature rupture of membranes, the emphasis has not been on the wound healing capacity of the fetal membranes. In this review, the relevant literature on the pathophysiologic condition that leads to preterm premature rupture of membranes will be summarized to emphasize a continuum of events between rupture and repair. We will present the current knowledge on fetal membrane wound healing and discuss the clinical implications of these findings. We will critically discuss recent experimental interventions in women to seal or heal the fetal membranes after preterm premature rupture of membranes.