Toll-like receptor 3 L412F polymorphism promotes a persistent clinical phenotype in pulmonary sarcoidosis.

BACKGROUND/INTRODUCTION: Sarcoidosis is a multi-systemic disorder of unknown etiology, characterized by the presence of non-caseating granulomas in target organs. In 90% of cases, there is thoracic involvement. Fifty to seventy percent of pulmonary sarcoidosis patients will experience acute, self-limiting disease. For the subgroup of patients who develop persistent disease, no targeted therapy is currently available. AIM: To investigate the potential of the single nucleotide polymorphism (SNP), Toll-like receptor 3 Leu412Phe (TLR3 L412F; rs3775291), as a causative factor in the development of and in disease persistence in pulmonary sarcoidosis. To investigate the functionality of TLR3 L412F in vitro in primary human lung fibroblasts from pulmonary sarcoidosis patients. DESIGN: SNP-genotyping and cellular assays, respectively, were used to investigate the role of TLR3 L412F in the development of persistent pulmonary sarcoidosis. METHODS: Cohorts of Irish sarcoidosis patients (n = 228), healthy Irish controls (n = 263) and a secondary cohort of American sarcoidosis patients (n = 123) were genotyped for TLR3 L412F. Additionally, the effect of TLR3 L412F in primary lung fibroblasts from pulmonary sarcoidosis patients was quantitated following TLR3 activation in the context of cytokine and type I interferon production, TLR3 expression and apoptotic- and fibroproliferative-responses. RESULTS: We report a significant association between TLR3 L412F and persistent clinical disease in two cohorts of Irish and American Caucasians with pulmonary sarcoidosis. Furthermore, activation of TLR3 in primary lung fibroblasts from 412 F-homozygous pulmonary sarcoidosis patients resulted in reduced IFN-ß and TLR3 expression, reduced apoptosis- and dysregulated fibroproliferative-responses compared with TLR3 wild-type patients. DISCUSSION/CONCLUSION: This study identifies defective TLR3 function as a previously unidentified factor in persistent clinical disease in pulmonary sarcoidosis and reveals TLR3 L412F as a candidate biomarker.

Sarcoidosis, alveolar ß-actin and pulmonary fibrosis.

BACKGROUND: Sarcoidosis is a multisystem granulomatous disease of unknown aetiology. Proteins present within the alveolar space early in sarcoidosis disease may provide an insight into novel mechanisms for the development of fibrotic disease and in particular pulmonary fibrosis. METHODS: A modified two-dimensional difference gel electrophoresis protocol was applied to the human bronchoalveolar lavage fluid (hBALF) of four patients with non-persistent pulmonary interstitial disease at 4-year follow-up (defined as mild disease) and four patients who developed pulmonary interstitial disease at 4-year follow-up (defined as severe disease). The protein ß-actin was identified by LC-MS/MS from a preparative gel and found to be significantly elevated in early lavages from the severe disease group. To look at the potential pro-fibrotic effects of this protein, primary human pulmonary fibroblasts (CCD-19Lu) were treated with recombinant ß-actin following which qPCR and ELISA assays were used to measure any effects. RESULTS: We found that ß-actin levels were significantly elevated in early hBALF samples in patients who subsequently developed severe disease when compared to the mild group. Treating primary human pulmonary fibroblasts with recombinant ß-actin led to enhanced gene expression of the pro-fibrotic markers alpha smooth muscle actin and collagen 1 as well as the increased secretion of interleukin-13 and metalloproteinases 3 and 9. CONCLUSION: Free ß-actin within the lungs of sarcoidosis patients potentially may contribute to disease pathogenesis particularly in the context of abnormal remodelling and the development of pulmonary fibrosis.

Male circumcision for HIV prevention in Papua New Guinea: a summary of research evidence and recommendations for public health following a national policy forum.

In 2005, a clinical trial in South Africa found that circumcision of young men could reduce their risk of acquiring HIV (human immunodeficiency virus) infection by over 60%. In the following year, two more trials in Africa confirmed this finding, leading the World Health Organization to recommend male circumcision as a public health strategy for HIV prevention in high-incidence countries. In order to inform public health policy in Papua New Guinea (PNG), two major research projects were initiated with the goals of investigating the status of penile cutting practices and assessing understandings, acceptability, feasibility and cost-effectiveness of male circumcision for HIV prevention. In addition, behavioural surveillance surveys systematically asked questions on penile cutting practices and an ethnographic literature review informed historical perspectives of penile cutting in PNG. Key findings from these research activities were presented at a National Policy Forum on Male Circumcision for HIV Prevention held in Port Moresby in November 2011. The Forum made three key recommendations: (1) the formation of a joint National Department of HealthlNational AIDS Council Secretariat Policy Committee on male circumcision; (2) the establishment of an integrated harm reduction program; and (3) that future policy on wide-scale roll-out of male circumcision for HIV prevention in PNG be informed by a combination of data from (a) male circumcision intervention pilot programs and (b) research on the potential protective effect of other forms of penile cutting.

Health workers, health facilities and penile cutting in papua new guinea: implications for male circumcision as an HIV prevention strategy.

There has been increasing interest in Papua New Guinea (PNG) in male circumcision (MC) for HIV (human immunodeficiency virus) prevention following compelling evidence from ecological studies and clinical trials in Africa, and the World Health Organization's recommendation in 2007 that MC be considered part of comprehensive HIV prevention programs in high-prevalence settings. Though no national policy has been established in PNG, East Sepik Province (ESP) commenced a formal program of MC in 2006, and there is evidence that PNG health workers are involved in other penile foreskin cutting activities in many areas. As part of a wider Male Circumcision Acceptability and Impact Study in PNG, we conducted an audit at a sample of PNG health facilities to assess their suitability for implementing a national MC program, and to identify issues that may arise in any future roll-out. The clinical audits demonstrated the difficulties with procurement and availability of equipment for general services around PNG, shortage of staff and capacity, and limitations of available clinical space. Results show that the ESP program has been successful; however, the success relies heavily on commitment from key workers to volunteer their time and services. A review of penile cutting activities by health care workers outside of the ESP program showed that the PNG health system is already involved in contemporary and traditional penile cutting practices via formal and informal arrangements: for example, by responding to complications from penile cuts performed by non-health workers, assisting community members to perform penile cutting through provision of equipment and advice, or providing regular penile foreskin cutting services for contemporary and traditional practices.

Effects of progressive resistive exercise in adults living with HIV/AIDS: systematic review and meta-analysis of randomized trials.

This systematic review examined the effectiveness and safety of progressive resistive exercise (PRE) interventions on immunological/virological, cardiopulmonary, weight, and body composition, strength and psychological outcomes in adults living with HIV. Using Cochrane Collaboration protocol, we included randomized controlled trials from 1980-2006 comparing PRE interventions with no PRE or another intervention. Ten studies met inclusion criteria. Seventeen meta-analyses were performed. Results indicated that PRE or a combination of PRE and aerobic exercise may lead to statistically significant increases in weight (WMD: 2.68 kg; 95%CI: 0.40, 4.97) and arm and thigh girth (WMD: 7.91 cm; 95%CI: 2.18, 13.65) among exercisers versus non-exercisers. Trends toward improvement in submaximum heart rate and exercise time also were found. Individual studies suggested that PRE contributed to improved strength and psychological status. Findings are limited to participants who continued to exercise. Progressive resistive exercise appears to be safe and may be beneficial for medically-stable adults living with HIV.

Patient support and education for promoting adherence to highly active antiretroviral therapy for HIV/AIDS.

BACKGROUND: Adherence to prescribed regimens is required to derive maximal benefit from many highly active antiretroviral therapy (HAART) regimens in people living with HIV/AIDS. OBJECTIVES: To conduct a systematic review of the research literature on the effectiveness of patient support and education to improve adherence to HAART. SEARCH STRATEGY: A systematic search of electronic databases was performed from January 1996 to May 2005. SELECTION CRITERIA: Randomized controlled trials examining the effectiveness of patient support and education to improve adherence to HAART were considered for inclusion. Only those studies that measured adherence at a minimum of six weeks were included. DATA COLLECTION AND ANALYSIS: Study selection, quality assessments and data abstraction were performed independently by two reviewers. MAIN RESULTS: Nineteen studies involving a total of 2,159 participants met criteria for inclusion. It was not possible to conduct a meta-analysis due to study heterogeneity with respect to populations, interventions, comparison groups, outcomes, and length of follow-up. Sample sizes ranged from 22 to 367. The populations studied ranged from general HIV-positive populations to studies focusing exclusively on children, women, Latinos, or adults with a history of alcohol dependence, to studies focusing almost exclusively on men. Study interventions included cognitive behavioral therapy, motivational interviewing, medication management strategies, and interventions indirectly targeting adherence, such as programs directed to reduce risky sexual behaviours. Ten studies demonstrated a beneficial effect of the intervention on adherence. We found that interventions targeting practical medication management skills, those administered to individuals vs groups, and those interventions delivered over 12 weeks or more were associated with improved adherence outcomes. We also found that interventions targeting marginalized populations such as women, Latinos, or patients with a past history of alcoholism were not successful at improving adherence. We were unable to determine whether effective adherence interventions were associated with improved virological or immunological outcomes. Most studies had several methodological shortcomings leaving them vulnerable to potential biases. AUTHORS' CONCLUSIONS: We found evidence to support the effectiveness of patient support and education interventions intended to improve adherence to antiretroviral therapy. Interventions targeting practical medication management skills, those interventions administered to individuals vs groups, and those interventions delivered over 12 weeks or more were associated with improved adherence outcomes. There is a need for standardization and increased methodological rigour in the conduct of adherence trials.

Setting and organization of care for persons living with HIV/AIDS.

BACKGROUND: Treating the world's 40.3 million persons currently infected with HIV/AIDS is an international responsibility that involves unprecedented organizational challenges. Key issues include whether care should be concentrated or decentralized, what type and mix of health workers are needed, and which interventions and mix of programs are best. High volume centres, case management and multi-disciplinary care have been shown to be effective for some chronic illnesses. Application of these findings to HIV/AIDS is less well understood. OBJECTIVES: Our objective was to evaluate the association between the setting and organization of care and outcomes for people living with HIV/AIDS. SEARCH STRATEGY: Computerized searches from January 1, 1980 to December 31, 2002 of MEDLINE, EMBASE, Dissertation Abstracts International (DAI), CINAHL, HealthStar, PsychInfo, PsychLit, Social Sciences Abstracts, and Sociological Abstracts as well as searches of meeting abstracts and relevant journals and bibliographies in articles that met inclusion criteria. Searches included articles published in English and other languages. SELECTION CRITERIA: Articles were considered for inclusion if they were observational or experimental studies with contemporaneous comparison groups of adults and/or children currently infected with HIV/AIDS that examined the impact of the setting and/or organization of care on outcomes of mortality, opportunistic infections, use of HAART and prophylaxis, quality of life, health care utilization, and costs for patient with HIV/AIDS. DATA COLLECTION AND ANALYSIS: Two authors independently screened abstracts to determine relevance. Full paper copies were reviewed against the inclusion criteria. The findings were extracted by both authors and compared. The 28 studies that met inclusion criteria were too disparate with respect to populations, interventions and outcomes to warrant meta-analysis. MAIN RESULTS: Twenty-eight studies were included involving 39,776 study subjects. The studies indicated that case management strategies and higher hospital and ward volume of HIV-positive patients were associated with decreased mortality. Case management was also associated with increased receipt of ARVs. The results for multidisciplinary teams or multi-faceted treatment varied. None of the studies examined quality of life or immunological or virological outcomes. Healthcare utilization outcomes were mixed. AUTHORS' CONCLUSIONS: Certain settings of care (i.e. high volume of HIV positive patients) and models of care (i.e. case management) may improve patient mortality and other outcomes. More detailed descriptions of care models, consistent definition of terms, and studies on innovative models suitable for developing countries are needed. There is not yet enough evidence to guide policy and clinical care in this area.

Aerobic exercise interventions for adults living with HIV/AIDS.

BACKGROUND: The profile of HIV infection is constantly changing. Although once viewed as an illness progressing to death, among those with access to antiretroviral therapy, HIV can now present as a disease with an uncertain natural history, perhaps a chronic manageable disease for some. This increased chronicity of HIV infection has been mirrored by increased prevalence of disablement in the HIV-infected population (Rusch 2004). Thus, the needs of these individuals have increasingly included the management of impairments (problems with body function or structure as a significant deviation or loss, such as pain or weakness), activity limitations (difficulties an individual may have in executing activities, such as inability to walk) and participation restrictions (problems an individual may experiences in involvement in life situations, such as inability to work) (WHO 2001). Exercise is a key strategy employed by people living with HIV/AIDS and by rehabilitation professionals to address these issues. Exercise has been shown to improve strength, cardiovascular function and psychological status in seronegative populations (Bouchard 1993), but what are the effects of exercise for adults living with HIV? If the risks and benefits of exercise for people living with HIV are better understood, appropriate exercise may be undertaken by those living with HIV/AIDS and appropriate exercise prescription may be practiced by healthcare providers. If effective and safe, exercise may enhance the effectiveness of HIV management, thus improving the overall outcome for adults living with HIV. OBJECTIVES: To examine the safety and effectiveness of aerobic exercise interventions on immunological/virological, cardiopulmonary and psychological parameters in adults living with HIV/AIDS. SEARCH STRATEGY: To identify the appropriate studies, we conducted a search using MEDLINE, EMBASE, SCIENCE CITATION INDEX, AIDSLINE, CINAHL, HEALTHSTAR, PSYCHLIT, SOCIOFILE, SCI, SSCI, ERIC and DAI. We also reviewed both published and unpublished abstracts and proceedings from major international and national HIV/AIDS conferences such as the Intersciences Conference on Antimicrobial Agents and Chemotherapy (ICAAC), the Conference on Retroviruses and Opportunistic Infections (CROI), the Infectious Diseases Society of America Conference (IDSA) and the International AIDS Conference (IAC). Reference lists from pertinent articles and books were reviewed and personal contacts with authors were used, as well as Collaborative Review Group databases. Targeted journals were handsearched for relevant articles. There were no language restrictions. Searches for the original review covered the period from 1980 to July 1999. The first update of this review included an additional search of the literature, followed by identification of included studies that met the inclusion criteria from August 1999 to January 2001. For the second update, we conducted a search to identify additional studies published from February 2001 to August 2003. SELECTION CRITERIA: Studies were included if they were randomized controlled trials (RCTs) comparing aerobic exercise interventions with no aerobic exercise interventions or another exercise or treatment modality, performed at least three times per week for at least four weeks among adults (18 years of age or older) living with HIV/AIDS. DATA COLLECTION AND ANALYSIS: Data on study design, participants, interventions, outcomes and methodological quality were abstracted from studies that met the inclusion criteria onto specifically designed data collection forms by at least two reviewers. Meta-analysis was conducted using RevMan 4.2 computer software on outcomes whenever possible. MAIN RESULTS: A total of 10 studies (six from the original search, two from the first updated search and two from this second updated search) met the inclusion criteria for this review. Main results indicated that performing constant or interval aerobic exercise, or a combination of constant aerobic exercise and progressive resistive exercise for at least 20 minutes, at least three times per week for four weeks appears to be safe and may lead to significant reductions in depressive symptoms and potentially clinically important improvements in cardiopulmonary fitness. These findings are limited to those participants who continued to exercise and for whom there was adequate follow-up data. AUTHORS' CONCLUSIONS: Aerobic exercise appears to be safe and may be beneficial for adults living with HIV/AIDS. These findings are limited by the small sample sizes and large withdrawal rates of the included studies. Future research would benefit from an increased attention to participant follow-up and intention-to-treat analysis. Further research is required to determine the optimal parameters of aerobic exercise and stage of disease in which aerobic exercise may be most beneficial for adults living with HIV.

Progressive resistive exercise interventions for adults living with HIV/AIDS.

BACKGROUND: Due to medical advancements, many people living with HIV infection in developed countries are living longer (Palella 1998). HIV infection can now present as a chronic illness with an uncertain natural disease history. The changing course of HIV infection has lead to a potential increase in the prevalence and impact of disability in people living with HIV infection. Exercise is one key management strategy used by health care professionals to address impairments (problems with body function or structure as a significant deviation or loss such as pain or weakness), activity limitations (difficulties an individual may have in executing activities such as inability to walk) and participation restrictions (problems an individual may experience in life situations such as inability to work) in this population (World Health Organization 2001). Exercise may also be used to address unwanted changes in weight and body composition in people living with HIV infection. Aerobic exercise has been associated with improvements in strength, cardiovascular function, and psychological status in general populations (Bouchard 1993). Results of a systematic review suggested that aerobic exercise interventions appeared to be safe and may lead to improvements in cardiopulmonary fitness for adults living with HIV/AIDS (Nixon 2002). But what are the effects of progressive resistive exercise (PRE) for adults living with HIV infection?A better understanding of the effectiveness and safety of progressive resistive exercise will enable people living with HIV and their health care workers to practice effective and appropriate exercise prescription, thus contributing to improved overall outcomes for adults living with HIV infection. OBJECTIVES: To examine the safety and effectiveness of progressive resistive exercise interventions on weight, body composition, strength, immunological/virological, cardiopulmonary and psychological parameters in adults living with HIV infection. SEARCH STRATEGY: To identify studies to be included in this review, we searched the following databases: MEDLINE, EMBASE, CINAHL, COCHRANE, SCIENCE CITATION INDEX, PSYCHINFO, SOCIOLOGICAL ABSTRACTS, SSCI, ERIC, DAI and HEALTHSTAR. We also reviewed both published and unpublished abstracts and proceedings from major international and national HIV/AIDS conferences such as the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), the Conference on Retroviruses and Opportunistic Infections (CROI), the Infectious Diseases Society of America Conference (IDSA), and the International AIDS Conference (IAC). Reference lists from pertinent articles and books were reviewed, as well as Collaborative Review Group databases. Targeted journals were also hand searched for relevant articles. No language restriction was applied. The search strategy covered literature from 1980-August 2003. SELECTION CRITERIA: We included studies that were randomized controlled trials (RCTs) comparing progressive resistive exercise interventions with no progressive resistive exercise or another exercise or treatment modality, performed at least three times per week, and lasting at least four weeks among adults (18 years of age or older) living with HIV/AIDS. DATA COLLECTION AND ANALYSIS: Data collection forms were used by reviewers to abstract data pertaining to study design, participants, interventions, outcomes and methodological quality from the studies that met inclusion criteria. Whenever possible, meta-analyses were conducted on outcomes using RevMan 4.2.2 computer software. MAIN RESULTS: Seven studies met the inclusion criteria for this systematic review. Meta-analysis was limited due to the following differences among the studies: types of exercise interventions, inclusion of co-intervention groups, level of exercise supervision, baseline body composition and testosterone levels of participants, types of outcomes assessed, and methodological quality of the individual studies.Main results indicated that performing progressive resistive exercise or a combination of progressive resistive exercise and aerobic exercise at least three times a week for at least four weeks appears to be safe and may lead to statistically and possibly clinically important increases in body weight and composition. Results also indicate exercise interventions may lead to clinically important improvements in cardiopulmonary fitness. Individual studies included in this review suggest that progressive resistive exercise interventions with or without aerobic exercise also contribute to improvements in strength and psychological status for adults living with HIV/AIDS. Individual studies indicate that progressive resistive exercise or a combination of progressive resistive and aerobic exercise appears to be safe for adults living with HIV/AIDS who are medically stable as a result of no change seen in immunological/virological status. These results are limited to those who continued to exercise and for whom there were adequate follow-up data. REVIEWERS' CONCLUSIONS: Progressive resistive exercise or a combination of progressive resistive exercise and aerobic exercise appear to be safe and may be beneficial for adults living with HIV/AIDS. These findings are limited by the small number of studies that could be included in meta-analyses, small sample sizes and variable participant withdrawal rates among included studies. Future research would benefit from including participants at various stages of HIV infection, a greater proportion of female participants, and participants in a variety of age groups to increase the generalizability of results. Furthermore, future research would benefit from studies with larger sample sizes that conduct an "intention-to-treat" analysis (analysis of participants based on the groups to which they were originally allocated) to better understand outcomes of participants that withdraw from exercise interventions.

The North Dublin randomized controlled trial of structured diabetes shared care.

BACKGROUND: A new diabetes shared care service was introduced in North Dublin. It was designed as a randomized controlled trial with a complex intervention comprising education of participating practitioners, the introduction of a community-based diabetes nurse specialist, local agreement on clinical protocols and structured communication across the primary-secondary care interface. OBJECTIVES: Our aim was to assess the feasibility and effectiveness of a structured diabetes shared care service in a mixed health care system and to analyse the impact on total patient care. METHODS: A Cluster randomized controlled trial lasting 18 months was carried out in 183 patients with type 2 diabetes from 30 general practices in North Dublin. Biophysical outcomes (HbA1c, blood pressure, body mass index), psychosocial measures (smoking status and Diabetes Clinic Treatment Satisfaction and Diabetes Well-being scores) and process outcomes were collected. RESULTS: There were significant improvements in diabetes care delivery and in psychosocial outcomes, but no significant improvements in biomedical outcomes. Process data collection revealed a significant increase in diabetes care-related activity for participating patients with an increase in structured annual reviews and fewer patients defaulting from care. There were also significant improvements in information exchange between primary and secondary care. CONCLUSION: Structured diabetes shared care, in a mixed health care system, can produce significant improvements in diabetes care delivery and in psychosocial outcomes for patients, with improved information exchange across the primary-secondary care interface.

A qualitative investigation of the views and health beliefs of patients with Type 2 diabetes following the introduction of a diabetes shared care service.

AIMS: A qualitative research approach was adopted in order to explore the views and health beliefs of patients with Type 2 diabetes who had experienced a new structured diabetes shared care service. METHODS: Patients from 15 general practices were randomly selected and invited to attend three focus groups. Two independent researchers adopted the "Framework" technique to analyse the transcribed data and identify key themes expressed by patients. RESULTS: Themes relating to diabetes included frustration, victimization and powerlessness in relation to living with diabetes, controlling blood sugar, medication and economic barriers to care. Differences in emphases between patients and healthcare providers emerged. Patients were generally positive about shared care and largely identified it with the nurses involved. CONCLUSION: This research highlights the importance of an in-depth exploration of patients' views during changes in diabetes care delivery to identify service delivery failures and gaps in patient knowledge such as lack of awareness of the extent of macrovascular risk.

Aerobic exercise interventions for adults living with HIV/AIDS.

BACKGROUND: The profile of HIV infection is constantly changing. Although once viewed as an illness progressing to death, among those with access to antiretroviral therapy, HIV infection can now present as a disease with an uncertain natural history, perhaps a chronic manageable disease for some. Thus, the needs of persons infected with HIV have increasingly included management of impairments, disabilities and handicaps. Exercise is a key management strategy employed by rehabilitation professionals to address these issues and assist persons living with HIV/AIDS. Exercise has been shown to improve strength, cardiovascular function, and psychological status in seronegative populations (~~Bouchard 1993~~) but what are the effects of exercise for adults living with HIV infection? If the risks and benefits of exercise for people living with HIV infection are better understood, appropriate exercise prescription may be practiced by health care providers, and may enhance the effectiveness of HIV management, thus improving the overall outcome for adults living with HIV infection. OBJECTIVES: To examine the effect of aerobic exercise interventions on cardiopulmonary, immunological/virological and psychological parameters in adults living with HIV infection. SEARCH STRATEGY: To identify the appropriate studies, we conducted a search using MEDLINE, EMBASE, SCIENCE CITATION INDEX, AIDSLINE, CINAHL, HEALTHSTAR, PSYCHLIT, SOCIOFILE, SCI, SSCI, ERIC and DAI. We also reviewed abstracts from international AIDS, ICAAC, and other major meetings. Reference lists from pertinent articles and books and personal contact with authors were also used, as were Collaborative Review Group databases and results of hand searching of targeted journals. All languages were included. Searches for the original review covered the period from 1980 to July 1999. For the purposes of this update, an additional literature search, following the same identification of studies criteria as listed above, was conducted from August 1999 to January 2001. SELECTION CRITERIA: To be selected, studies had to be randomized controlled trials involving HIV+ adults 18 years of age or older and had to include at least one group randomized to receive aerobic exercise performed at least three times/week for at least four weeks. DATA COLLECTION AND ANALYSIS: Data on study design, participants, interventions, and outcomes were extracted from the reports onto specifically designed data collection forms by at least two reviewers. MAIN RESULTS: A total of eight studies (six from the original search and two from the updated search) were identified that satisfied the eligibility criteria. The main results indicated that performing constant or interval aerobic exercise, or a combination of constant aerobic exercise and progressive resistive exercise for at least 20 minutes, at least three times per week for four weeks appears to be safe and may lead to clinically significant improvements in cardiopulmonary fitness. Furthermore, individual studies suggest that aerobic exercise may improve psychological well-being for adults living with HIV/AIDS. These findings are limited to those who continued to exercise and for whom there was adequate follow-up data. REVIEWER'S CONCLUSIONS: Aerobic exercise appears to be safe and may be beneficial for adults living with HIV/AIDS. These findings are limited by the small sample sizes and large drop-out rates of the included studies. Future research would benefit from an increased attention to participant follow-up and intention-to-treat analysis. Further research is required to determine the optimal parameters of aerobic exercise and stage of disease in which aerobic exercise may be most beneficial for adults living with HIV infection.

The North Dublin Diabetes Shared Care (DiSC) Project: a profile of current diabetes care in Ireland.

The DiSC Project aims to assess the feasibility, effectiveness and costs of diabetes shared care in Ireland. Baseline results provide a profile of diabetes care in Ireland. Thirty general practices are participating in this randomised controlled trial. Outcomes include biophysical and psychosocial measures. The majority of patients agreed to participate in diabetes shared care. Data was collected from 183 patients with type 2 diabetes. The mean age of the patients is 65 years, 56% are male and 63% are GMS eligible. The mean HBA1c was 6.8% though 21% of patients had a HBA1c>8%. The majority of patients had a blood pressure, total cholesterol and body mass index above recommended guidelines. Only half the patients are attending a dietician or a chiropodist. The majority of patients have good glycaemic control but poor blood pressure and cholesterol control. The full trial results will determine if a shared care approach can improve clinical and psychosocial outcomes for patients.

The management of invasive transitional cell carcinoma of the bladder. Results of definitive and preoperative radiation therapy in 390 patients treated at the Prince of Wales Hospital, Sydney, Australia.

The treatment results for invasive transitional cell carcinoma (TCC) of the bladder were assessed in a series of 390 patients referred to the Department of Radiation Oncology at the Prince of Wales Hospital, Sydney, Australia, during the period 1977 to 1988. These patients were managed by one of two strategies: cystectomy (87 patients) and radiation therapy (303 patients). Actuarial survival rates (death from any cause) were determined and comparisons were made using log-rank tests and Cox regression analyses. The mean follow-up time was 7.6 years. Independent prognostic factors for shorter survival were: the presence of a ureteric obstruction (P less than 0.001), increasing clinical stage (P less than 0.001), increasing patient age (P = 0.003), and earlier year of presentation (P = 0.008). Comparison of the two strategies indicated no significant difference in overall survival after adjusting for imbalances in prognostic factors (P = 0.007 unadjusted; P = 0.29 adjusted). The slightly longer survival of 46 patients from 1983 onward who received primary systemic chemotherapy (compared with 149 patients not given chemotherapy) was not statistically significant (P = 0.12 unadjusted; P = 0.56 adjusted for prognostic factors). The 5-year actuarial rates of severe complications were 8.0% after cystectomy and 5.3% after radiation therapy. In 303 patients treated by definitive radiation therapy, the 5-year actuarial rate of freedom from bladder failure for all clinical tumor stages was 44% (Tx, 67%; T1, 45%; T2, 56%; T3, 39%; and T4, 39%). These results suggest that definitive radiation therapy is a viable alternative to radical cystectomy for patients with invasive TCC of the bladder.

Results of radiotherapy for localised prostatic carcinoma treated at the Prince of Wales Hospital, Sydney.

Between 1980 and 1986 a total of 218 patients with localised prostatic carcinoma received radical pelvic radiotherapy at The Prince of Wales Hospital, Sydney. The mean follow-up time was 4.6 years. The five-year actuarial overall survival rate was 63% (death from all causes) and the five-year cancer-specific survival rate was 73% (death from or with prostate cancer). The overall survival was significantly worse with more advanced clinical stage of the disease (P = 0.003) and with poor histological differentiation of the tumour (P = 0.001). The five-year actuarial rate for local control of tumour in the pelvis was 84%. Late treatment-related complications (occurring or persisting beyond six months) were mild or moderate and the majority settled with conservative management. Only five patients experienced severe complications (necessitating surgical treatment). Of 42 patients with normal potency documented before radiotherapy who were not subsequently hormonally manipulated 23 (55%) retained potency at two years. These results for definitive radiotherapy for localised prostatic carcinoma indicate good local control with minimal morbidity and compare favourably with other published results.

Bowel complications after radiotherapy for carcinoma of the prostate: the volume effect.

Late radiation-induced bowel complications were studied in 218 patients treated for localized carcinoma of the prostate by radical radiotherapy at the Prince of Wales Hospital between 1980 and 1986. Mild to moderate toxicity was seen in 38 cases, and severe toxicity requiring surgery occurred in 3 patients. The total actuarial complication rate (by 5 years) for all grades was 24% and for severe complications was 1.8%. Significant patient-related risk factors were older age at the time of radiotherapy (p = 0.035) and a previous history of abdominal operations (p = 0.028). Among treatment-related risk factors only inclusion of the whole pelvis in the irradiated volume had a significant association with this complication (p = 0.015). The risk of bowel complications was not related to the total radiation dose or to the use of interstitial implants as employed in this series.