LIMPRINT: prevalence of chronic edema in health services in Copenhagen, Denmark

Background: The International Lymphedema Framework developed an international study, Lymphedema Impact and Prevalence International (LIMPRINT) to estimate the prevalence and impact of chronic edema in heterogeneous populations. Methods and results: A validation study using the LIMPRINT methodology was undertaken in Denmark. Participants with CO were identified from in-patient services and compared to those identified within a specialist lymphoedema service and 3 primary care settings. Of 452 inpatients available for screening CO was present in 177(39%) and absent in 275(61%). In addition, 723 participants were found from specialist and primary care services (LPCS). In-patients were significantly older and more likely to be underweight or normal weight. They were more likely to suffer from heart failure/IHD (44.6% vs 23.4%, p<0.001) and have neurological problems (18.1% vs 10.9% p=0.009). The inpatient group were nearly all suffering from secondary Lymphoedema and were less likely to have a cancer or venous diagnosis, but more likely to have immobility as the cause of CO (44.0% vs 17.7%, p<0.001). No in-patients had midline CO compared to 30 within LPCS. Fewer in the in-patient group had standard CO treatment (17.1% vs 73.5%, p<0.001) and subjective control of swelling was worse (19.9% vs 66.7%, p<0.001). Whilst the in-patient group experienced fewer acute infections, when they did so, they were more likely to be admitted to hospital for this (78.6% vs 51.0%, p=0.049). Conclusion: The prevalence of CO in inpatient facilities is high and those with CO have multiple comorbidities that vary according to setting. The feasibility study showed the methodology could be adapted for use in different health systems

Hypothermia and Fever After Organophosphorus Poisoning in Humans—A Prospective Case Series

There have been many animal studies on the effects of organophosphorus pesticide (OP) poisoning on thermoregulation with inconsistent results. There have been no prospective human studies. Our aim was to document the changes in body temperature with OP poisoning. A prospective study was conducted in a rural hospital in Polonnaruwa, Sri Lanka. We collected data on sequential patients with OP poisoning and analyzed 12 patients selected from 53 presentations who had overt signs and symptoms of OP poisoning and who had not received atropine prior to arrival. All patients subsequently received specific management with atropine and/or pralidoxime and general supportive care. Tympanic temperature, ambient temperature, heart rate, and clinical examination and interventions were recorded prospectively throughout their hospitalization. Initial hypothermia as low as 32°C was observed in untreated patients. Tympanic temperature increased over time from an early hypothermia (<35°C in 6/12 patients) to later fever (7/12 patients >38°C at some later point). While some of the late high temperatures occurred in the setting of marked tachycardia, it was also apparent that in some cases fever was not accompanied by tachycardia, making excessive atropine or severe infection an unlikely explanation for all the fevers. In humans, OP poisoning causes an initial hypothermia, and this is followed by a period of normal to high body temperature. Atropine and respiratory complications may contribute to fever but do not account for all cases

LIMPRINT in Australia

Background and study objective: Australia was one of nine participating countries in the epidemiology Phase II LIMPRINT project to determine the number of people with chronic oedema in local health services. Methods and results: Data collection occurred through questionnaire-based interviews and clinical assessment with provided LIMPRINT tools. Four different types of services across three states in Australia participated. A total of 222 adults participated with an age range from 22 to 102 years, and 60% were female. Site 1 included three residential care facilities (54% of participants had swelling), site 2 was community delivered aged care services (24% of participants had swelling), site 3 was a hospital setting (facility-based prevalence study) (28% of participants had swelling) and site 4 was a wound treatment centre (specific patient population) (100% of participants had swelling). Of those with chronic oedema or secondary lymphoedema 93% were not related to cancer, the lower limbs were affected in 51% of cases and 18% of participants with swelling reported one or more episodes of cellulitis in the previous year. Wounds were identified in 47% (n=105) of all participants with more than half of those with wounds coming from the dedicated wound clinic. Leg/foot ulcer was the most common type of wound (65% n=68). Conclusion: Distances between services, lack of specialised services and various state funding models contribute to inequities in CO treatment. Understanding the high number of non-cancer related chronic oedema presentations will assist health services to provide timely, effective care and improve referral pathways

Proteinase-Activated Receptor-1, CCL2 and CCL7 Regulate Acute Neutrophilic Lung Inflammation

PAR1 plays a central role in mediating the interplay between coagulation and inflammation, but its role in regulating acute neutrophilic inflammation is unknown. We report that antagonism of PAR1 was highly effective at reducing acute neutrophil accumulation in a mouse model of LPS-induced lung inflammation. PAR1 antagonism also reduced alveolar-capillary barrier disruption in these mice. This protection was associated with a reduction in the expression of the chemokines CCL2 and CCL7, but not the pro-inflammatory cytokines TNF and IL-6 or the classic neutrophil chemoattractants CXCL1 and CXCL2. Antibody neutralisation of CCL2 and CCL7 significantly reduced LPS-induced total leukocyte and neutrophil accumulation, recovered from the bronchoalveolar lavage fluid of challenged mice. Immunohistochemical analysis revealed CCL2 predominantly localised to alveolar macrophages and pulmonary epithelial cells, while CCL7 was restricted to the pulmonary epithelium. In keeping with these observations, the intranasal administration of rCCL2 and rCCL7 led to the accumulation of neutrophils within the lung airspaces of naïve mice in the absence of any underlying inflammation. Flow cytometry analysis further demonstrated an increase in Ly6Ghi neutrophils expressing the chemokine receptors CCR1 and CCR2 isolated from mouse lungs compared to circulating neutrophils. Conversely, the expression of CXCR2 decreased on neutrophils isolated from the lung compared to circulating neutrophils. Furthermore, this switch in chemokine receptor expression was accentuated following acute LPS-induced lung inflammation. Collectively, these findings reveal a novel role for PAR1 and the chemokines CCL2 and CCL7 during the early events of acute neutrophilic inflammation

Clinical and ethical challenges in undertaking LIMPRINT in vulnerable populations

Background and study objective: To estimate the prevalence of CO and wounds within two vulnerable populations a male, high security prison in the East Midlands (UK) and residential and nursing homes in the UK and Australia. Methods and results: Methods for screening for chronic oedema (CO) and wounds were adapted from the main LIMPRINT methodology. Prison population. In total, 195 inmates were recruited with 22(11%) having CO. While the majority were white Caucasian (156 / 83.4%) a further 20 (10.7%) were dark skinned with 11 (5.95%) from other minority populations. Co-morbidities included 123 (63%) smokers, 22 (11%) alcohol dependant, 60 (31%) with mental health problems and 35 (18%) a history of self- harm. Only three had a current wound with 30 (16%) having had a traumatic stab wound. Residential and nursing homes (UK and Australia): In the UK, the total population available for inclusion was 189 with only 137(73%) recruited. Seventy two of the 137 (52%) suffered from CO and a further 16 (23%) had a history of cellulitis. Results from the Australian residential care facilities have been published in full. In summary, of the 37 participants 20 (54%) experienced CO with 25 (68%) having co-morbidities and 11 (30%) having a concurrent wound. Conclusion: Obtaining an accurate picture of the prevalence and impact of CO in vulnerable populations is extremely challenging due issues of access and consent. Lack of reliable data for these populations will contribute to poor service provision

LIMPRINT: the UK experience - subjective control of swelling in patients attending specialist lymphedema services

Background and study design: This study was undertaken as part of the UK LIMPRINT international study to determine the number of people with chronic oedema and its impact on health services. Overall 7436 with chronic oedema (CO) were recruited in the main UK study from a range of health settings. Methods and results: Subjective control of arm and leg chronic oedema (CO) was defined for patients attending three Lymphoedema services in the UK. Of the total available in the UK dataset 5165 (69.4%)/ 7436(100%) of participants were included. Reasons for exclusions included the following: lack of information (1669), having both arm and leg swelling (272), lack of description of control (5) and professional inability to decide whether CO was controlled (325). Arm swelling occurred in 953 (18.5%), with leg CO in 4212 (81.5%). Poor control was found in 1430 (27.7%) and good control in 3735 (72.3%). Control of arm swelling was worse in men and control increased overall in those aged over 45 years. In contrast control of CO worsened in those with leg CO with increasing age and multiple co-morbidities. Obesity and cellulitis, particularly an episode in the last year were associated with poor control. Independent risk factors for arm CO were obesity, neurological disease and cellulitis in the last year and for leg CO: obesity, poor mobility, heart disease, presence of a wound, cellulitis in the last year and duration of swelling. Conclusion: Control of CO within specialised centres is complex due to sociodemographic and clinical comorbidities

Manual lymphatic drainage therapy in patients with breast cancer related lymphoedema

<p>Abstract</p> <p>Background</p> <p>Lymphoedema is a common and troublesome condition that develops following breast cancer treatment. The aim of this study is to analyze the effectiveness of Manual Lymphatic Drainage in the treatment of postmastectomy lymphoedema in order to reduce the volume of lymphoedema and evaluate the improvement of the concomitant symptomatology.</p> <p>Methods</p> <p>A randomized, controlled clinical trial in 58 women with post-mastectomy lymphoedema. The control group includes 29 patients with standard treatment (skin care, exercise and compression measures, bandages for one month and, subsequently, compression garnments). The experimental group includes 29 patients with standard treatment plus Manual Lymphatic Drainage. The therapy will be administered daily for four weeks and the patient's condition will be assessed one, three and six months after treatment.</p> <p>The primary outcome parameter is volume reduction of the affected arm after treatment, expressed as a percentage. Secondary outcome parameters include: duration of lymphoedema reduction and improvement of the concomitant symptomatology (degree of pain, sensation of swelling and functional limitation in the affected extremity, subjective feeling of being physically less atractive and less feminine, difficulty looking at oneself naked and dissatisfaction with the corporal image).</p> <p>Discussion</p> <p>The results of this study will provide information on the effectiveness of Manual Lymphatic Drainage and its impact on the quality of life and physical limitations of these patients.</p> <p>Trial registration</p> <p>ClinicalTrials (NCT): <a href="http://www.clinicaltrials.gov/ct2/show/NCT01152099">NCT01152099</a></p

Estimation of the prevalence of lymphoedema/chronic oedema in acute hospital in-patients

Background: To estimate the prevalence of lymphoedema/chronic oedema and wounds in acute hospital in-patients in 5 different countries. Method: A point-prevalence study was carried out during working day periods in six general hospitals in four countries (Denmark, France, United Kingdom, Australia) and one hospital oncology in-patient unit in one other country (Ireland). The study used validated clinical tools for the assessment and collection of data. Data were collected by expert clinicians through interviews and physical examination of the patients present in the wards. Results: A total of 1905 patients could be included and investigated among the 3041 total bed occupancy in the seven hospitals. Lymphoedema/chronic oedema was present in 723 of them (38%). Main risk factors associated with chronic oedema were age, morbid obesity and heart failure as well as chair bound immobility and neurological deficiency. History of cellulitis was frequent in patients with chronic oedema and wounds (24.8%), chronic oedema alone (14.1%) as compared to the 1.5% prevalence in patients without chronic oedema. Conclusion: Lymphoedema/chronic oedema is very frequent in patients hospitalized in hospital acute wards. It is strongly associated with obesity, venous insufficiency and heart failure. Our results strongly suggest a hidden health care burden and cost linked to chronic oedema independently of chronic wounds

A genome-wide association study identifies protein quantitative trait loci (pQTLs)

There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10 -57), CCL4L1 (p = 3.9×10-21), IL18 (p = 6.8×10-13), LPA (p = 4.4×10-10), GGT1 (p = 1.5×10-7), SHBG (p = 3.1×10-7), CRP (p = 6.4×10-6) and IL1RN (p = 7.3×10-6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10-40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways. © 2008 Melzer et al

Psychological determinants of whole-body endurance performance

Background: No literature reviews have systematically identified and evaluated research on the psychological determinants of endurance performance, and sport psychology performance-enhancement guidelines for endurance sports are not founded on a systematic appraisal of endurance-specific research. Objective: A systematic literature review was conducted to identify practical psychological interventions that improve endurance performance and to identify additional psychological factors that affect endurance performance. Additional objectives were to evaluate the research practices of included studies, to suggest theoretical and applied implications, and to guide future research. Methods: Electronic databases, forward-citation searches, and manual searches of reference lists were used to locate relevant studies. Peer-reviewed studies were included when they chose an experimental or quasi-experimental research design, a psychological manipulation, endurance performance as the dependent variable, and athletes or physically-active, healthy adults as participants. Results: Consistent support was found for using imagery, self-talk, and goal setting to improve endurance performance, but it is unclear whether learning multiple psychological skills is more beneficial than learning one psychological skill. The results also demonstrated that mental fatigue undermines endurance performance, and verbal encouragement and head-to-head competition can have a beneficial effect. Interventions that influenced perception of effort consistently affected endurance performance. Conclusions: Psychological skills training could benefit an endurance athlete. Researchers are encouraged to compare different practical psychological interventions, to examine the effects of these interventions for athletes in competition, and to include a placebo control condition or an alternative control treatment. Researchers are also encouraged to explore additional psychological factors that could have a negative effect on endurance performance. Future research should include psychological mediating variables and moderating variables. Implications for theoretical explanations of endurance performance and evidence-based practice are described