Recruiting and retaining GPs and patients in intervention studies: the DEPS-GP project as a case study

Background  

Recruiting and retaining GPs for research can prove difficult, and may result in sub-optimal patient participation where GPs are required to recruit patients. Low participation rates may affect the validity of research.     

Molecular pathology of prostate cancer

The molecular pathology of prostate cancer is complex; not only are multiple genes involved in its pathogenesis, but additional environmental factors such as diet and inflammation are also involved. The exhaustive research into prostate cancer to date has demonstrated a complex interaction of multiple genes and environmental factors, some of which may be more important in individual prostate cancer cases. This is an exciting era, with the emergence of new investigative tools such as DNA microarray technology and the application of the field of proteomics to the study of human cancers. Knowledge of genetic changes underlying the initiation, development, and progression of prostate cancer is accumulating rapidly. With increasing knowledge, it may be possible to distinguish indolent from aggressive prostate tumours by molecular fingerprinting. This review discusses the most consistently reported molecular pathological findings in hereditary and sporadic prostate cancer, together with new concepts and technologies.     

Cellular localisation of HHV-8 in Castleman's disease: is there a link with lymph node vascularity?

AIMS: Human herpesvirus 8 (HHV-8) has been identified in multicentric Castleman's disease and in angioimmunoblastic lymphadenopathies. However, the presence of the virus does not necessarily indicate an aetiological role in these conditions. This study investigates the cell types infected by HHV-8 in Castleman's disease and examines the correlation between HHV-8 and Castleman's disease lymph node angiogenesis. METHODS: Sixteen formalin fixed, paraffin wax embedded samples from patients with Castleman's disease (six multicentric, 10 solitary) were examined for the presence of HHV-8 using the polymerase chain reaction (PCR), non-isotopic in situ hybridisation, PCR in situ hybridisation (PCR-ISH), and real time quantitative TaqMan PCR to HHV-8 open reading frame 26 (ORF-26), and viral (v)-cyclin encoding regions. Vascularity was assessed using CD34, CD31, and factor VIII immunocytochemistry, and lymph nodes were scored as "low" or "high". RESULTS: Five multicentric Castleman's disease and two solitary Castleman's disease biopsies were positive for HHV-8. HHV-8 was identified in approximately 10% of intranodal B lymphocytes, in endothelial cells, and in subcapsular spindle cell proliferations. The copy number of HHV-8 was low at 10-50 copies/1000 cells. The highest copy number was in subcapsular spindle cells. There was no correlation between vascularity score and HHV-8 status. CONCLUSION: The preferential localisation of HHV-8 in subcapsular spindle cell proliferations (where early intranodal Kaposi's sarcoma initiates) and endothelial cells in Castleman's disease might finally explain the link between intranodal Kaposi's sarcoma and Castleman's disease.     

Nebulization of Fluids of Different Physicochemical Properties with Air-Jet and Ultrasonic Nebulizers

Purpose. Empirical formulae relate the mean size of primary droplets from jet and ultrasonic nebulizers to a fluid's physicochemical properties. Although the size selective filtering effects of baffling and evaporation may modify the secondary aerosol produced, this research sought to evaluate whether viscosity and surface tension of nebulized fluids influenced the aerosol's size and output characteristics. Methods. Fluid systems of different surface tension and viscosity (glycerol and propylene glycol solutions [10–50% (v/v)] and a range of silicone fluids [200/0.65 cs– l00cs]) were nebulized in three jet and two ultrasonic nebulizers. Secondary aerosol characteristics were measured with a Malvern 2600C laser diffraction sizer and the nebulization times, residual volumes and percentage outputs were determined. Results. While the droplet size appeared to be inversely proportional to viscosity for jet nebulizers, it was directly proportional to viscosity for ultrasonic nebulizers. Although fluid systems with lower surface tensions generally produced slightly smaller MMDs, the relationship between surface tension and droplet size was complex. The more viscous fluids required longer nebulization times and were associated with increased residual amounts (lower outputs). The ultrasonic nebulizers did not effectively, and were on occasion unable to, nebulize the more viscous fluids. Conclusions. It follows that there are cut-off values for viscosity and/or surface tension above or below which ultrasonic devices fail to operate. Moreover, jet nebulizers generated an aerosol with an optimum respirable output from median-viscosity fluids.     

The estimated costs and savings of medical nutrition therapy: the Medicare population

OBJECTIVES: To measure the potential savings from medical nutrition therapy (MNT) and to estimate the net cost to Medicare of covering these services for Medicare enrollees. This includes developing an estimate of the cost of providing medical nutrition services to the Medicare population and estimating the savings in hospital and other spending resulting from the use of these services. DESIGN: Analysis of longitudinal data from the Group Health Cooperative of Puget Sound (Seattle, Wash) for persons aged 55 years and older who have coverage for MNT services. SUBJECTS/SETTING: Persons aged 55 years and older who had diabetes (n = 12,308), cardiovascular disease (n = 10,895), or renal disease (n = 3,328) and who were covered under the Group Health Cooperative of Puget Sound, including Medicare beneficiaries enrolled in the plan's Medicare risk contract program. Extrapolation to the US Medicare population is based on data for persons served by the Group Health Cooperative of Puget Sound. INTERVENTION: The use of MNT. MAIN OUTCOMES MEASURE: Differences in health care utilization levels of persons with diabetes, cardiovascular disease, and renal disease who do and do not receive MNT. Differences in utilization were estimated for hospital discharges per calendar quarter, physician visits per quarter, and other outpatient visits per quarter. STATISTICAL ANALYSES PERFORMED: Multivariate regression models of changes in utilization for persons after they receive MNT services. RESULTS: Our analysis showed that MNT was associated with a reduction in utilization of hospital services of 9.5% for patients with diabetes and 8.6% for patients with cardiovascular disease. Also, utilization of physician services declined by 23.5% for MNT users with diabetes and 16.9% for MNT users with cardiovascular disease. The net cost of covering MNT under Medicare is estimated to be $369.7 million over the 1998 through 2004 period. The total cost of benefits is estimated to be $2.7 billion over this period. This would be partially offset by estimated savings of $2.3 billion resulting in net costs of $369.7 million. The program would actually yield net savings after the third year of the program, which would continue through 2004 and beyond. CONCLUSION: After an initial period of implementation, coverage for MNT can result in a net reduction in health services utilization and costs for at least some populations. In the case of persons aged 55 years and older, the savings in utilization of hospital and other services will actually exceed the cost of providing the MNT benefit. These results suggest that Medicare coverage of MNT has the potential to pay for itself with savings in utilization for other services.     

Sham radiation in clinical trials assessing radiotherapy for exudative age-related macular degeneration

BACKGROUND: To evaluate the effectiveness of sham radiation treatments in masking patients to their randomization group in the Radiation of Age-Related Macular Degeneration (ROARMD) Study. METHODS: Patients with choroidal neovascularization complicating age-related macular degeneration were randomized to a treatment (RAD) group that received external beam irradiation (seven treatment sessions) or to a control (SHAM) group that received sham radiation (one sham treatment session). During a telephone survey, 62 of 73 randomized patients responded to the following questions: Do you think you received radiation? Why do you feel that way? Did the vision in your study eye worsen after enrollment? RESULTS: Eighty-one percent of the RAD group and 59% of the SHAM group thought that they had received radiation. In patients who thought that their vision had stabilized or improved, 82% thought that they had received radiation. In patients who thought that their vision was worse, only 39% thought that they had received radiation. In 54% of patients, subjective perception of vision influenced their guess as to whether they received radiation. CONCLUSIONS: Subjective patient perception of visual outcome was the most influential variable for masking. Variation between radiation treatment and sham session techniques, such as equipment used and duration of treatments, played a lesser role in the masking of patients. Seven treatment days correlated with a higher number of patients who thought that they had received radiation. Although our procedures do not strictly mask the two groups, one sham radiation session was effective in keeping patients guessing their randomization group.     

dPQL: a lossless distributed algorithm for generalized linear mixed model with application to privacy-preserving hospital profiling

ObjectiveTo develop a lossless distributed algorithm for generalized linear mixed model (GLMM) with application to privacy-preserving hospital profiling.Materials and MethodsThe GLMM is often fitted to implement hospital profiling, using clinical or administrative claims data. Due to individual patient data (IPD) privacy regulations and the computational complexity of GLMM, a distributed algorithm for hospital profiling is needed. We develop a novel distributed penalized quasi-likelihood (dPQL) algorithm to fit GLMM when only aggregated data, rather than IPD, can be shared across hospitals. We also show that the standardized mortality rates, which are often reported as the results of hospital profiling, can also be calculated distributively without sharing IPD. We demonstrate the applicability of the proposed dPQL algorithm by ranking 929 hospitals for coronavirus disease 2019 (COVID-19) mortality or referral to hospice that have been previously studied.ResultsThe proposed dPQL algorithm is mathematically proven to be lossless, that is, it obtains identical results as if IPD were pooled from all hospitals. In the example of hospital profiling regarding COVID-19 mortality, the dPQL algorithm reached convergence with only 5 iterations, and the estimation of fixed effects, random effects, and mortality rates were identical to that of the PQL from pooled data.ConclusionThe dPQL algorithm is lossless, privacy-preserving and fast-converging for fitting GLMM. It provides an extremely suitable and convenient distributed approach for hospital profiling.