Danielle Crawley

Impact of pay for performance on quality of chronic disease management by social class group in England

Summary Objective To examine associations between social class and achievement of selected national audit targets for coronary heart disease (CHD), diabetes and hypertension in England before and after the introduction of a major pay for performance programme in 2004. Design Secondary analysis of 2003 and 2006 national survey data for respondents with CHD and diabetes and hypertension. Setting England. Main outcome measure Achievement of national audit targets for blood pressure, blood glucose and cholesterol control. Results There were no significant differences in achievement of blood pressure targets in individuals from manual and non-manual occupational groups with diabetes (2003: 65.9% v 60.3%, 2006: 67.6% v 69.7%) or hypertension (2003: 66.2% v 66.2%, 2006: 72.8% v 71.9%) before or after the introduction of pay for performance. Achievement of the cholesterol target was also similar in individuals from manual and non-manual groups with diabetes (2003: 52.5% v 46.6%, 2006: 68.7% v 70.5%) or CHD (2003: 54.3% v 53.3%, 2006: 68.6% v 71.3%). Differences in achievement of the blood pressure target in CHD [75.8% v 84.5%; AOR 0.44 (0.21-0.90)] were evident between manual and non-manual occupational groups after the introduction of pay for performance. Conclusion The quality of chronic disease management in England was broadly equitable between socioeconomic groups before this major pay for performance programme and remained so after its introduction.

Quantifying the Evidence for the Risk of Metabolic Syndrome and Its Components following Androgen Deprivation Therapy for Prostate Cancer: A Meta-Analysis

Background No meta-analysis is yet available for the risk of metabolic syndrome (MetS) following androgen deprivation therapy (ADT) for men with prostate cancer. To summarize the evidence for the link between ADT and MetS or its components quantitatively with a meta-analysis including all studies published to date. Methods PubMed and Embase were searched using predefined inclusion criteria to perform meta-analyses on the association between metabolic syndrome, hyperglycemia, diabetes, hypertension, dyslipidemia or obesity and androgen deprivation therapy in patients with prostate cancer. Random effects methods were used to estimate pooled relative risks (RRs) and 95% confidence intervals (CI). Results A total of nine studies was included. There was a positive association between ADT and risk of MetS (RR: 1.75 (95% CI: 1.27–2.41)). Diabetes was the only MetS component present in more than 3 studies, and also showed an increased risk following ADT (RR: 1.36 (95% CI: 1.17–1.58)). Conclusion This is the first quantitative summary addressing the potential risk of MetS following ADT in men with PCa. The positive RRs indicate that there is a need to further elucidate how type and duration of ADT affect these increased risks of MetS and diabetes as the number of men with PCa treated with ADT is increasing.

Anti-Angiogenic Effect of Bortezomib in Patients with Multiple Myeloma

with MM, treated with bortezomib. The patients studied (6 males/3 females; median age 58 years, range 34–72 years) had previously received more than 4 lines of treatment, including high-dose melphalan treatment with autologous stem cell support, and had relapsed before bortezomib administration. Six patients had IgG MM, while 1 patient had IgA, 1 non-secretory and 1 light-chain MM. Bortezomib was given at a dose of 1.3 mg/m 2 , intravenously, in 3-week cycles, on days 1, 4, 8 and 11 of each cycle, for at least 8 cycles. Microvessel density (MVD) was assessed in bone marrow trephine biopsies before treatment and after 4 and 8 cycles of treatment. Immunohistochemistry was performed on paraffi n sections with commercially available monoclonal mouse antibodies to CD34 (QBEND-10, Dako, Denmark). Antibody localization was performed using the Super SensitiveTM immunohistochemistry detection system (Biogenix, USA) with diaminobenzidine as the fi nal substrate. The sections were independently assessed by two pathologists. The numbers of CD34stained blood vessels were counted using an eyepiece graticule under 200 ! magnifi cation. The counts were performed in the areas of the marrow infi ltrated by myeloma cells. The counts were fi nally expressed as number of vessels per 1 mm 2 area of the involved marrow. In cases where there was a difference greater than 20% between the counts performed by the two pathologists, the counts Bortezomib (Velcade ® ) is a proteasome inhibitor, which has been proved to be very effective for the treatment of multiple myeloma (MM) in phase II and III clinical trials [1–3] . Bortezomib produces a rapid anti-myeloma effect, which has led to tumour lysis syndrome in approximately 1% of myeloma patients [4, 5] . Although the mechanism of cell death via bortezomib is likely multifactorial, myeloma cell seems particularly sensitive to inhibition of the nuclear factor B (NFB) pathway. Bortezomib prevents NFB activation by blocking the degradation of its inhibitor I B. Blocking NFB transcriptional activity, bortezomib enhances myeloma cell apoptosis and leads to reduced levels of growth factors, angiogenic factors and cell adhesion molecules, which are crucial for the growth and survival of myeloma cells [6, 7] . Furthermore, bortezomib affects intracellular regulatory molecules, such as p53, p21 and p27, blocks the antiapopoptic effects of bcl-2, inhibits DNA repair and restores the sensitivity of MM cells to doxorubicin and melphalan [7] . In vivo preclinical studies on mice have shown that bortezomib has an anti-angiogenic activity as well [8] . The aim of this study was to investigate whether bortezomib has an anti-angiogenic effect in patients with MM and whether that correlates with response to treatment. We studied the effect of bortezomib on angiogenesis in bone marrow biopsies and serum samples of 9 patients Received: March 9, 2005 Accepted: March 10, 2005

Association between duration and type of Androgen Deprivation Therapy and risk of diabetes in men with prostate cancer

Androgen deprivation therapy (ADT) for prostate cancer (PCa) increases risk of type 2 diabetes (T2DM); however the association between types and duration of ADT has not been fully elucidated. We examined how type and duration of ADT affects risk of T2DM. Using data from Prostate Cancer database Sweden (PCBaSe) we investigated risk of T2DM in a cohort of 34,031 men with PCa on ADT; i.e., anti‐androgens (AA), orchiectomy, or gonadotropin‐releasing hormone (GnRH) agonists compared to an age‐matched, PCa‐free comparison cohort (n = 167,205) using multivariate Cox proportional hazard regression. T2DM was defined as a newly filled prescription for metformin, sulphonylurea, or insulin in the Prescribed Drug Register. A total of 21,874 men with PCa received GnRH agonists, 9,143 AA and 3,014 underwent orchiectomy. Risk of T2DM was increased in men in the GnRH agonists/orchiectomy group during the first 3 years of ADT [i.e., 1 − 1.5 years HR: 1.61 (95%CI: 1.36 − 1.91)], compared to PCa‐free men. The risk decreased thereafter (e.g., 3 − 4 years HR: 1.17 (95% CI: 0.98 − 1.40)). Conversely, no increased risk was seen in men on AA (HR: 0.74 (95%CI: 0.65 − 0.84). The incidence of T2DM per 1,000 person‐years was 10 for PCa‐free men, 8 for men on AA, and 13 for men on GnRH agonists/orchiectomy. Duration of ADT has a significant impact on risk of T2DM. With the peak after three years of treatment, our data indicates that men on ADT, even for a limited period of time, such as adjuvant to radiotherapy, are at increased risk of T2DM.

Association between type 2 diabetes, curative treatment and survival in men with intermediate- and high-risk localized prostate cancer

To investigate whether curative prostate cancer (PCa) treatment was received less often by men with both PCa and Type 2 diabetes mellitus (T2DM) as little is known about the influence of T2DM diagnosis on the receipt of such treatment in men with localized PCa.

A systematic review of the literature exploring the interplay between prostate cancer and type two diabetes mellitus

Prostate cancer (PCa) and type two diabetes mellitus (T2DM) are both increasing prevalent conditions and often occur concurrently. However, the relationship between the two is more complex than just two prevalent conditions co-existing. This review systematically explores the literature around the interplay between the two conditions. It covers the impact of pre-existing T2DM on PCa incidence, grade and stage, as well as exploring the impact of T2DM on PCa outcomes and mortality and the interaction between T2DM and PCa treatments.

Does a prostate cancer diagnosis affect management of pre-existing diabetes? Results from PCBaSe Sweden: a nationwide cohort study

Objectives Both prostate cancer (PCa) and type 2 diabetes mellitus (T2DM) are increasingly prevalent conditions, which frequently coexist in men. Here, we set out to specifically examine the impact of a PCa diagnosis and its treatment on T2DM treatment. Setting This study uses observational data from Prostate Cancer database Sweden Traject. Participants The study was undertaken in a cohort of 16 778 men with T2DM, of whom 962 were diagnosed with PCa during mean follow-up of 2.5 years. Primary and secondary outcome measures We investigated the association between PCa diagnosis and escalation in T2DM treatment in this cohort. A treatment escalation was defined as a new or change in anti-T2DM prescription, as recorded in the prescribed drug register (ie, change from diet to metformin or sulphonylurea or insulin). We also investigated how PCa diagnosis was associated with two treatment escalations. Multivariate Cox proportional hazards regression with age as a time scale was used while adjusting for educational level and initial T2DM treatment. Results We found no association between PCa diagnosis and risk of a single treatment escalation (HR 0.99, 95% CI 0.87 to 1.13). However, PCa diagnosis was associated with an increased risk of receiving two consecutive T2DM treatment escalations (HR 1.75, 95% CI 1.38 to 2.22). This increase was strongest for men on gonadotropin-releasing hormone (GnRH) agonists (HR 3.08, 95% CI 2.14 to 4.40). The corresponding HR for men with PCa not on hormonal treatment was 1.40 (95% CI 1.03 to 1.92) and for men with PCa on antiandrogens 0.91 (95% CI 0.29 to 2.82). Conclusions Men with T2DM who are diagnosed with PCa, particularly those treated with GnRH agonists, were more likely to have two consecutive escalations in T2DM treatment. This suggests a need for closer monitoring of men with both PCa and T2DM, as coexistence of PCa and its subsequent treatments could potentially worsen T2DM control.

Drugs for metabolic conditions and prostate cancer death in men on GnRH agonists.

To evaluate whether drugs for metabolic conditions influence prostate cancer‐specific mortality in men starting gonadotrophin‐releasing hormone (GnRH) agonists, as it is unclear whether metabolic syndrome and its related drugs is affecting treatment response in men with prostate cancer on GnRH agonists.

Epidemiology of Bladder Cancer

Bladder cancer is the ninth commonest cancer in the world with over 400,000 cases diagnosed each year of which 90 % are Transitional Cell Carcinomas (TCC). Bladder cancer incidence varies globally, with the highest rates seen in Europe, North America, North Africa, and the Middle East. It has a higher incidence in males than females and its incidence rises steeply after the age of 50. Smoking is the most important risk factor for development of bladder cancer, with smokers having up to four times higher risk than non-smokers. Many occupational exposures have also been associated with higher risk of bladder cancer. Clinically bladder cancer is divided into non-muscle-invasive, muscle-invasive, and metastatic disease. Patients most commonly present with painless haematuria and the gold standard diagnostic test is a cystoscopy followed by a ‘transurethral resection of bladder tumor’ to obtain a histological diagnosis. Treatment depends upon the stage of the disease. The primary treatment for non-muscle-invasive bladder cancer is a transurethral resection of bladder tumor (TURBT) followed by adjuvant treatment with either chemotherapy or Bacillus Calmette–Guerin (BCG) immunotherapy. For muscle-invasive disease the gold standard treatment is a radical cystectomy with lymph node dissection, with 5-year survival around 50 %. Some patients may also receive neoadjuvant cisplatin based chemotherapy. The primary treatment for advanced or metastatic disease is chemotherapy doublet combinations including cisplatin. There are limited second or third line treatments for these patients though recent results using immunotherapy have proved promising.