Mapping Local Failure Following Bladder Radiotherapy According to Dose.

AIMS: To determine the relationship between local relapse following radical radiotherapy for muscle-invasive bladder cancer (MIBC) and radiation dose. MATERIALS AND METHODS: Patients with T2-4N0-3M0 MIBC were recruited to a phase II study assessing the feasibility of intensity-modulated radiotherapy to the bladder and pelvic lymph nodes. Patients were planned to receive 64 Gy/32 fractions to the bladder tumour, 60 Gy/32 fractions to the involved pelvic nodes and 52 Gy/32 fractions to the uninvolved bladder and pelvic nodes. Pre-treatment set-up was informed by cone-beam CT. For patients who experienced local relapse, cystoscopy and imaging (CT/MRI) was used to reconstruct the relapse gross tumour volume (GTVrelapse) on the original planning CT . GTVrelapse D98% and D95% was determined by co-registering the relapse image to the planning CT utilising deformable image registration (DIR) and rigid image registration (RIR). Failure was classified into five types based on spatial and dosimetric criteria as follows: A (central high-dose failure), B (peripheral high-dose failure), C (central elective dose failure), D (peripheral elective dose failure) and E (extraneous dose failure). RESULTS: Between June 2009 and November 2012, 38 patients were recruited. Following treatment, 18/38 (47%) patients experienced local relapse within the bladder. The median time to local relapse was 9.0 months (95% confidence interval 6.3-11.7). Seventeen of 18 patients were evaluable based on the availability of cross-sectional relapse imaging. A significant difference between DIR and RIR methods was seen. With the DIR approach, the median GTVrelapse D98% and D95% was 97% and 98% of prescribed dose, respectively. Eleven of 17 (65%) patients experienced type A failure and 6/17 (35%) patients type B failure. No patients had type C, D or E failure. MIBC failure occurred in 10/17 (59%) relapsed patients; of those, 7/11 (64%) had type A failure and 3/6 (50%) had type B failure. Non-MIBC failure occurred in 7/17 (41%) patients; 4/11 (36%) with type A failure and 3/6 (50%) with type B failure. CONCLUSION: Relapse following radiotherapy occurred within close proximity to the original bladder tumour volume and within the planned high-dose region, suggesting possible biological causes for failure. We advise caution when considering margin reduction for future reduced high-dose radiation volume or partial bladder radiotherapy protocols.

Vision impairment and cognitive function among urban-dwelling malaysians aged 55 years and over from the Malaysian Elders Longitudinal Research (MELoR) study.

INTRODUCTION: Published literature on vision impairment and cognitive function amongst older Malaysians remains scarce. This study investigates the association between vision impairment and cognitive function in an older Malaysian population. METHODS: Subjects aged 55 years and above from the Malaysian Elders Longitudinal Research (MELoR) study with available information on vision and Montreal Cognitive Assessment (MoCA) scores were included. Data were obtained through a home-based interview and hospital-based health check by trained researchers. Visual acuity (VA) was assessed with logMAR score with vision impairment defined as VA 6/18 or worse in the better-seeing eye. Cognition was evaluated using the MoCA-Blind scoring procedure. Those with a MoCA-Blind score of <19/22 were considered to have cognitive impairment. RESULTS: Data was available for 1144 participants, mean (SD) age = 68.57 (±7.23) years. Vision impairment was present in 143 (12.5 %) and 758 (66.3 %) had MoCA-Blind score of <19. Subjects with vision impairment were less likely to have a MoCA-Blind score of ≥19 (16.8 % vs 36.2 %, p < 0.001). Vision impairment was associated with poorer MoCA-Blind scores after adjustments for age, gender, and ethnicity (ß = 2.064; 95 % CI, -1.282 to 3.320; P = 0.003). In those who had > 6 years of education attainment, vision impairment was associated with a significant reduction of cognitive function and remained so after adjustment for age and gender (ß = 1.863; 95 % CI, 1.081-3.209; P = 0.025). CONCLUSION: Our results suggest that vision impairment correlates with cognitive decline. Therefore, maintaining good vision is an important interventional strategy for preventing cognitive decline in older adults.

Risk factors associated with soil transmitted helminth (STH) infection in two indigenous communities in Malaysia.

Soil-transmitted helminth (STH) could possibly cause mild to severe health effects such as diarrhea, weakness, intestinal blood loss, and impaired cognitive development and growth. In Malaysia, previous studies depicted a high prevalence rate of STH was due to poor hygiene practice and low efficacies of anthelminthic drugs. This study was conducted to investigate hand hygiene practice and WASH criteria's (Water, sanitation and hygiene) related to STH infection among two indigenous tribes in Peninsular Malaysia. A cross-sectional study was carried out to study the relationship among STH infection compared to water quality, sanitation, and hygiene conditions. A total of 190 individuals from two indigenous villages participated in the study, with ages ranging from 5 to 60 years old. In addition, Pearson's Chisquare (X2) test was utilized to test the relationship among STH with demographic socioeconomic and behavioral factors. The confidence interval (CI) of 95% is used to estimate the precision of the odds ratio (OR). Multivariate logistic regression models were also used to identify the risk factors associated with STH infections. The overall findings indicated a prevalence rate of 72% for STH, and distributed mainly among children aged < 12 years. Furthermore, multivariate analyses using logistic regression revealed chronic health problems, incorrect hand washing, and walking bare footed were associated with STH infection. Overall results indicated high prevalence of STH among the indigenous villagers, which aligns with the published literature and proves to be a problem need to be addressed as neglected disease. Interestingly, there was a significant relationship between the presences of chronic diseases and STH infection, which prompted other questions the awareness needs to be educated and the simple and low-cost intervention on the proper way of hand washing may help to reduce STH infection in these indigenous communities.

The Intensity-Modulated Pelvic Node and Bladder Radiotherapy (IMPART) Trial: A Phase II Single-Centre Prospective Study.

AIMS: Node-positive bladder cancer (NPBC) carries a poor prognosis and has traditionally been treated palliatively. However, surgical series suggest that a subset of NPBC patients can achieve long-term control after cystectomy and lymph node dissection. There is little published data regarding the use of radiotherapy to treat NPBC patients. This is in part due to concerns regarding the toxicity of whole-pelvis radiotherapy using conventional techniques. We hypothesised that, using intensity-modulated radiotherapy (IMRT), the pelvic nodes and bladder could be treated within a radical treatment volume with acceptable toxicity profiles. MATERIALS AND METHODS: The Intensity-modulated Pelvic Node and Bladder Radiotherapy (IMPART) trial was a phase II single-centre prospective study designed to assess the feasibility of delivering IMRT to treat the bladder and pelvic nodes in patients with node-positive or high-risk node-negative bladder cancer (NNBC). The primary end point was meeting predetermined dose constraints. Secondary end points included acute and late toxicity, pelvic relapse-free survival and overall survival. RESULTS: In total, 38 patients were recruited and treated between June 2009 and November 2012; 22/38 (58%) had NPBC; 31/38 (81.6%) received neoadjuvant chemotherapy; 18/38 (47%) received concurrent chemotherapy; 37/38 (97%) patients had radiotherapy planned as per protocol. Grade 3 gastrointestinal and genitourinary acute toxicity rates were 5.4 and 20.6%, respectively. At 1 year, the grade 3 late toxicity rate was 5%; 1-, 2- and 5-year pelvic relapse-free survival rates were 55, 37 and 26%, respectively. The median overall survival was 1.9 years (95% confidence interval 1.1-3.8) with 1-, 2- and 5-year overall survival rates of 68, 50 and 34%, respectively. CONCLUSION: Delivering IMRT to the bladder and pelvic nodes in NPBC and high-risk NNBC is feasible, with low toxicity and low pelvic nodal recurrence rates. Long-term control seems to be achievable in a subset of patients. However, relapse patterns suggest that strategies targeting both local recurrence and the development of distant metastases are required to improve patient outcomes.

Risk factors associated with soil transmitted helminth (STH) infection in two indigenous communities in Malaysia

@#Soil-transmitted helminth (STH) could possibly cause mild to severe health effects such as diarrhea, weakness, intestinal blood loss, and impaired cognitive development and growth. In Malaysia, previous studies depicted a high prevalence rate of STH was due to poor hygiene practice and low efficacies of anthelminthic drugs. This study was conducted to investigate hand hygiene practice and WASH criteria’s (Water, sanitation and hygiene) related to STH infection among two indigenous tribes in Peninsular Malaysia. A cross-sectional study was carried out to study the relationship among STH infection compared to water quality, sanitation, and hygiene conditions. A total of 190 individuals from two indigenous villages participated in the study, with ages ranging from 5 to 60 years old. In addition, Pearson’s Chisquare (X2) test was utilized to test the relationship among STH with demographic socioeconomic and behavioral factors. The confidence interval (CI) of 95% is used to estimate the precision of the odds ratio (OR). Multivariate logistic regression models were also used to identify the risk factors associated with STH infections. The overall findings indicated a prevalence rate of 72% for STH, and distributed mainly among children aged < 12 years. Furthermore, multivariate analyses using logistic regression revealed chronic health problems, incorrect hand washing, and walking bare footed were associated with STH infection. Overall results indicated high prevalence of STH among the indigenous villagers, which aligns with the published literature and proves to be a problem need to be addressed as neglected disease. Interestingly, there was a significant relationship between the presences of chronic diseases and STH infection, which prompted other questions the awareness needs to be educated and the simple and low-cost intervention on the proper way of hand washing may help to reduce STH infection in these indigenous communities.

Prevalence and documented causes of hyponatraemia among geriatric patients attending a primary care clinic.

INTRODUCTION: Hyponatraemia is the commonest electrolyte abnormality and has major clinical implications. However, few studies of hyponatraemia in the primary care setting has been published to date. OBJECTIVES: To determine the prevalence, potential causes and management of hyponatraemia and to identify factors associated with severity of hyponatraemia among older persons in a primary care setting. METHODS: Electronic records were searched to identify all cases aged ≥60 years with a serum sodium <135mmol/l, attending outpatient clinic in 2014. Patients' medical records with the available blood test results of glucose, potassium, urea and creatinine were reviewed. RESULTS: Of the 21,544 elderly, 5873 patients (27.3%) had electrolyte profile tests. 403 (6.9%) had hyponatraemia in at least one blood test. Medical records were available for 253, mean age 72.9±7.3 years, 178 (70.4%) had mild hyponatraemia, 75 (29.6%) had moderate to severe hyponatraemia. Potential causes were documented in 101 (40%). Patients with moderate to severe hyponatraemia were five times more likely to have a cause of hyponatraemia documented (p<0.01). Medications were the commonest documented cause of hyponatraemia (31.7%). Hydrochlorothiazide use was attributed in 25 (78.1%) of 32 with medication-associated hyponatraemia. Repeat renal profile (89%) was the commonest management of hypotonic hyponatraemia. CONCLUSION: Whilst hyponatraemia was common in the clinic setting, many cases were not acknowledged and had no clear management strategies. In view of mild hyponatraemia has deleterious consequences, future studies should determine whether appropriate management of mild hyponatraemia will lead to clinical improvement.

Tai Chi with music improves quality of life among community-dwelling older persons with mild to moderate depressive symptoms: A cluster randomized controlled trial.

Depression leads to a poorer quality of life (QOL) which is a determinant of healthy ageing. Cost-effective solutions for enhancing QOL in the older population are much needed in China, with its rapidly ageing population. We conducted a randomized controlled trial involving 112 community-dwelling older participants with mild to moderate depression, to evaluate the effect of Tai Chi with music on QOL (57 in intervention group, 55 in control group). WHO Quality of Life-BREF was used to measure QOL at baseline and at every month for three months. Following the adjustments for sociodemographic data, the effect of intervention on QOL was assured (F = 25.145, P < 0.001, ηp2= 0.435, F = 18.696, P < 0.001, ηp2= 0.364, F = 17.473, P< 0.001, ηp2= 0.348, and F = 29.576, P < 0.001, ηp2= 0.475 for physical, psychological, social, and environment domains respectively). This intervention represents an economically viable solution to better QOL and healthy ageing in a highly populous developing nation.

Orientation and verbal fluency in the English Longitudinal Study of Ageing: modifiable risk factors for falls?

OBJECTIVES: To determine the relationship between falls and deficits in specific cognitive domains in older adults. DESIGN: An analysis of the English Longitudinal Study of Ageing (ELSA) cohort. SETTING: United Kingdom community-based. PARTICIPANTS: 5197 community-dwelling older adults recruited to a prospective longitudinal cohort study. MEASUREMENTS: Data on the occurrence of falls and number of falls, which occurred during a 12-month follow-up period, were assessed against the specific cognitive domains of memory, numeracy skills, and executive function. Binomial logistic regression was performed to evaluate the association between each cognitive domain and the dichotomous outcome of falls in the preceding 12 months using unadjusted and adjusted models. RESULTS: Of the 5197 participants included in the analysis, 1308 (25%) reported a fall in the preceding 12 months. There was no significant association between the occurrence of a fall and specific forms of cognitive dysfunction after adjusting for self-reported hearing, self-reported eyesight, and functional performance. After adjustment, only orientation (odds ratio [OR]: 0.80; 95% confidence intervals [CI]: 0.65-0.98, p = 0.03) and verbal fluency (adjusted OR: 0.98; 95% CI: 0.96-1.00; p = 0.05) remained significant for predicting recurrent falls. CONCLUSIONS: The cognitive phenotype rather than cognitive impairment per se may predict future falls in those presenting with more than one fall.

The Impact of Combined Music and Tai Chi on Depressive Symptoms Among Community-Dwelling Older Persons: A Cluster Randomized Controlled Trial.

BACKGROUND: The effectiveness of pharmacological treatment may be limited in older persons. Several studies using Tai Chi or music therapy separately confirmed positive effects in the reduction of depressive symptoms. We conducted a cluster randomized controlled trial to evaluate the possible synergistic effect of combined music and Tai Chi on depressive symptoms. METHODS: One hundred and seven older adults with mild to moderate depressive symptoms were recruited from Ya'an city. Fifty-five participants were cluster randomized to combined music and Tai Chi group for three months, while the other fifty-two individuals were randomized to the control group that entailed routine health education delivered monthly by community nurses. The primary outcome of depressive symptoms was measured with the Geriatric Depression Scale (GDS) at baseline and monthly for three months. RESULTS: At three-month follow-up, a statistically significant improvement in depressive symptoms was found in the intervention group compared with control group (F(3,315) = 69.661, P < 0.001). Following adjustments for socio-demographic data, the true effect of intervention on depressive symptoms was significant (F = 41.725, P < 0.01, ηp2 = 0.574). CONCLUSIONS: Combined music and Tai Chi reduced depressive symptoms among community-dwelling older persons. This represents an economically viable solution to the management of depression in highly populous developing nations.

Experience of a rapid access falls and syncope service at a teaching hospital in Kuala Lumpur.

No abstract available.

Falls amongst older people in Southeast Asia: a scoping review.

OBJECTIVES: The older population in the Southeast Asian region is accelerating and is expected to surpass the proportion of the ageing population in North America and Europe in the future. This study aims to identify the research literature related to falls among older people in Southeast Asia, to examine current practice and discuss the future direction on falls prevention and interventions in the region. STUDY DESIGN: A scoping review design was used. METHODS: A systematic literature search was conducted using the Medline, CINAHL, AMED, Ageline, PsycINFO, Web of Sciences, Scopus, Thai-Journal Citation Index, MyCite and trial registries databases. RESULTS: Thirty-seven studies and six study protocols were included, from Thailand, Malaysia, Singapore, Vietnam, Indonesia and the Philippines. One-sixth of the studies involved interventions, while the remainder were observational studies. The observational studies mainly determined the falls risk factors. The intervention studies comprised multifactorial interventions and single interventions such as exercises, educational materials and visual correction. Many of the studies replicated international studies and may not have taken into account features unique to Southeast Asia. CONCLUSION: Our review has revealed studies evaluating falls and management of falls in the Southeast Asian context. More research is required from all Southeast Asian countries to prepare for the future challenges of managing falls as the population ages.

Perceptions of Healthcare Professionals on the Usage of Percutaneous Endoscopic Gastrostomy in a Teaching Hospital from a Middle-Income South East Asian Country.

OBJECTIVE: To explore the perceptions of healthcare professionals' (HCPs) in a South East Asian nation towards percutaneous endoscopic gastrostomy (PEG) feeding. DESIGN: Semi-structured, qualitative interviews. SETTINGS: A teaching hospital in Kuala Lumpur, Malaysia. PARTICIPANTS: A total of 17 healthcare professionals aged 23-43 years, 82% women. RESULTS: Thematic analysis revealed five themes that represent HCPs' perceptions in relation to the usage of PEG feeding: 1) knowledge of HCPs, 2) communication, 3) understanding among patients, and 4) financial and affordability. CONCLUSION: The rationale for reluctance towards PEG feeding observed in this regions was explained by lack of education, knowledge, communication, team work, and financial support. Future studies should assess the effects of educational programmes among HCPs and changes in policies to promote affordability on the utilization of PEG feeding in this region.

Human leucocyte antigen class I-redirected anti-tumour CD4+ T cells require a higher T cell receptor binding affinity for optimal activity than CD8+ T cells.

CD4+ T helper cells are a valuable component of the immune response towards cancer. Unfortunately, natural tumour-specific CD4+ T cells occur in low frequency, express relatively low-affinity T cell receptors (TCRs) and show poor reactivity towards cognate antigen. In addition, the lack of human leucocyte antigen (HLA) class II expression on most cancers dictates that these cells are often unable to respond to tumour cells directly. These deficiencies can be overcome by transducing primary CD4+ T cells with tumour-specific HLA class I-restricted TCRs prior to adoptive transfer. The lack of help from the co-receptor CD8 glycoprotein in CD4+ cells might result in these cells requiring a different optimal TCR binding affinity. Here we compared primary CD4+ and CD8+ T cells expressing wild-type and a range of affinity-enhanced TCRs specific for the HLA A*0201-restricted NY-ESO-1- and gp100 tumour antigens. Our major findings are: (i) redirected primary CD4+ T cells expressing TCRs of sufficiently high affinity exhibit a wide range of effector functions, including cytotoxicity, in response to cognate peptide; and (ii) optimal TCR binding affinity is higher in CD4+ T cells than CD8+ T cells. These results indicate that the CD4+ T cell component of current adoptive therapies using TCRs optimized for CD8+ T cells is below par and that there is room for substantial improvement.

Is there an Ideal Breast Conservation Rate for the Treatment of Breast Cancer?

Since the results of randomised controlled trials in the last quarter of the twentieth century were reported, it has been conventionally accepted that breast conservation treatment (BCT) provides equivalent survival to mastectomy for early breast cancer. As expected, there was an initial fall in the use of mastectomy. The first decade of the twenty-first century, however, witnessed a trend of increasing mastectomy rates in some regions. This perplexing circumstance served as an impetus for a relook at survival outcomes with each surgical modality. Recent studies have demonstrated higher survival rates and improved local control associated with BCT. Such findings warrant a re-evaluation of treatment strategies, beginning with whether there is an optimum BCT rate.

Genotyping of microsatellite markers to study genetic structure of the wild striped snakehead Channa striata in Malaysia.

Genetic variability and differences in wild striped snakehead Channa striata from Malaysia were analysed by genotyping nine novel nuclear microsatellite loci. Analysis revealed moderate-to-high genetic diversity in most of the populations, indicative of large effective population sizes. The highly diversified populations are admixed populations and, therefore, can be recommended as potential candidates for selective breeding and conservation since they each contain most of the alleles found in their particular region. Three homogenous groups of the wild populations were identified, apparently separated by effective barriers, in accordance with contemporary drainage patterns. The highest population pairwise FST found between members of the same group reflects the ancient population connectivity; yet prolonged geographical isolation resulted in adaptation of alleles to local contemporary environmental change. A significant relationship between genetic distance and geographical isolation was observed (r = 0·644, P < 0·01). Anthropogenic perturbations indicated apparent genetic proximity between distant populations.

Anticholinergic burden is associated with recurrent and injurious falls in older individuals.

OBJECTIVE: While the anticholinergic activity of medications has been linked to cognitive decline, few studies have linked anticholinergic burden with falls in older people. We evaluated the relationship between anticholinergic burden and recurrent and injurious falls among community-dwelling older adults. STUDY DESIGN: This case-control study was performed on 428 participants aged ≥65 years, 263 cases with two or more falls or one injurious fall in the preceding 12 months, and 165 controls with no falls in the preceding 12 months. Anticholinergic burden was determined using the anticholinergic cognitive burden (ACB) scale. Upper and lower limb functional abilities were assessed with timed up and go (TUG), functional reach (FR) and grip strength (GS). Logistic regression analysis was employed to calculate the mediation effect of TUG, FR and GS on ACB associated falls. RESULTS: Univariate analysis revealed a significant association between an ACB score of ≥1 with falls (OR, 1.8; 95% CI; 1.1-3.0; p=0.01) and significantly poorer TUG and FR. The association between ACB≥1 and falls was no longer significant after adjustment for either TUG (OR for ACB associated falls, 1.4; 95% CI, 0.88-2.4; p=0.14) or FR (OR for ACB associated falls, 1.4; 95% CI, 0.89-2.4, p=0.12) but remained significant with GS. CONCLUSION: The association between recurrent and injurious falls and the use of any medications listed in the ACB scale was mediated through gait and balance impairment but not by muscular weakness, providing a novel insight into the potential mechanistic link between ACB and falls. Future studies should determine whether TUG and FR measurements could help inform risk to benefit decisions where ACB medications are being considered.

Percutaneous endoscopic gastrostomy versus nasogastric feeding in older individuals with non-stroke dysphagia: a systematic review.

OBJECTIVE: The objective of this systematic review was to evaluate existing studies on the effectiveness of percutaneous endoscopic gastrostomy (PEG) feeding compared to nasogastric (NG) feeding for patients with non-stroke related dysphagia. METHODS: We searched Ovid MEDLINE, EMBASE, the Cochrane Library, Web of Science and PubMed databases through to December 2013 using the terms "percutaneous endoscopic gastrostomy", "gastrostomy", "PEG", "nasogastric", "nasogastric tube", "nasogastric feeding" and "intubation". We included randomized controlled trials (RCTs) and non-RCTs which compared PEG with NG feeding in individuals with non-stroke dysphagia. RESULTS: 9 studies involving 847 participants were included in the final analysis, including two randomized trials. Pooled analysis indicated no significant difference in the risk of pneumonia [relative risk (RR) = 1.18, 95% confidence interval (CI) = 0.87-1.60] and overall complications [relative risk (RR) = 0.80, 95% confidence interval (CI) = 0.63-1.02] between PEG and NG feeding. A meta-analysis was not possible for mortality and nutritional outcomes, but three studies suggested improved mortality outcomes with PEG feeding while two out of three studies reported PEG feeding to be better from a nutritional perspective. CONCLUSIONS: Firm conclusions could not be derived on whether PEG feeding is beneficial over NG feeding in older persons with non-stroke dysphagia, as previously published literature were unclear or had a high risk of bias. A well-designed and adequately powered RCT, which includes carer strain and quality of life as outcome measures is therefore urgently needed.

T cell receptor binding affinity governs the functional profile of cancer-specific CD8+ T cells.

Antigen-specific T cell receptor (TCR) gene transfer via patient-derived T cells is an attractive approach to cancer therapy, with the potential to circumvent immune regulatory networks. However, high-affinity tumour-specific TCR clonotypes are typically deleted from the available repertoire during thymic selection because the vast majority of targeted epitopes are derived from autologous proteins. This process places intrinsic constraints on the efficacy of T cell-based cancer vaccines and therapeutic strategies that employ naturally generated tumour-specific TCRs. In this study, we used altered peptide ligands and lentivirus-mediated transduction of affinity-enhanced TCRs selected by phage display to study the functional properties of CD8(+) T cells specific for three different tumour-associated peptide antigens across a range of binding parameters. The key findings were: (i) TCR affinity controls T cell antigen sensitivity and polyfunctionality; (ii) supraphysiological affinity thresholds exist, above which T cell function cannot be improved; and (iii) T cells transduced with very high-affinity TCRs exhibit cross-reactivity with self-derived peptides presented by the restricting human leucocyte antigen. Optimal system-defined affinity windows above the range established for natural tumour-specific TCRs therefore allow the enhancement of T cell effector function without off-target effects. These findings have major implications for the rational design of novel TCR-based biologics underpinned by rigorous preclinical evaluation.

Home orthostatic training in chronic fatigue syndrome--a randomized, placebo-controlled feasibility study.

BACKGROUND: Orthostatic (Tilt)-training is an effective treatment for neurally mediated hypotension (NMH). NMH is a frequent finding in chronic fatigue syndrome (CFS). We evaluated home orthostatic training (HOT) in CFS in a randomized placebo-controlled feasibility study. METHODS: Thirty-eight patients with CFS (Fukuda Criteria) were randomly allocated to daily tilt training (n = 19) or sham training (n = 19) for 6 months. Haemodynamic responses to standing were performed in all subjects using continuous technology (Taskforce) at enrolment, week 1, 4 and 24. Symptom response and compliance were assessed using diaries. RESULTS: Two patients (one from each arm) withdrew from the study. Fourteen patients in each group complied completely or partially, and patients found the training manageable and achievable. Compared to the sham group, blood pressure while standing dropped to 8.0 mmHg less in the HOT group at 4 weeks (95% CI: 1.0 to 15.0, P = 0.03). At 4 weeks, the HOT group had higher total peripheral resistance compared to the sham group; mean difference 70.2, 95% CI: -371.4 to 511.8. Changes were maintained at 6 months. There was no significant difference in fatigue between groups at 4 weeks (mean difference 1.4, 95% CI: -13.5 to 16.2), but there was a trend towards improvement in fatigue at 6 months. Compliers had lower fatigue compared to non-compliers. CONCLUSIONS: A placebo-controlled study of HOT in CFS is feasible. HOT is well tolerated and generally complied with. A likely physiological rationale for HOT in CFS is related to reductions in orthostatic intolerance. An adequately powered study including strategies to enhance compliance is warranted.