Infectious Diseases Institute at Makerere University College of Health Sciences: a case study of a sustainable capacity building model for health care, research and training.

The Infectious Diseases Institute (IDI), established in 2001, was the first autonomous institution of Makerere University set up as an example of what self-governing institutes can do in transforming the academic environment to become a rapidly progressive University addressing the needs of society This paper describes the success factors and lessons learned in development of sustainable centers of excellence to prepare academic institutions to respond appropriately to current and future challenges to global health. Key success factors included a) strong collaboration by local and international experts to combat the HIV pandemic, along with b) seed funding from Pfizer Inc., c) longstanding collaboration with Accordia Global Health Foundation to create and sustain institutional strengthening programs, d) development of a critical mass of multi-disciplinary research leaders and managers of the center, and e) a series of strong directors who built strong governance structures to execute the vision of the institute, with subsequent transition to local leadership. Conclusion: Twenty years of sustained investment in infrastructure, human capital, leadership, and collaborations present Makerere University and the sub-Saharan Africa region with an agile center of excellence with preparedness to meet the current and future challenges to global health.

BOXIT-A Randomised Phase III Placebo-controlled Trial Evaluating the Addition of Celecoxib to Standard Treatment of Transitional Cell Carcinoma of the Bladder (CRUK/07/004).

BACKGROUND: Non-muscle-invasive bladder cancer (NMIBC) has a significant risk of recurrence despite adjuvant intravesical therapy. OBJECTIVE: To determine whether celecoxib, a cyclo-oxygenase 2 inhibitor, reduces the risk of recurrence in NMIBC patients receiving standard treatment. DESIGN, SETTING, AND PARTICIPANTS: BOXIT (CRUK/07/004, ISRCTN84681538) is a double-blinded, phase III, randomised controlled trial. Patients aged ≥18 yr with intermediate- or high-risk NMIBC were accrued across 51 UK centres between 1 November 2007 and 23 July 2012. INTERVENTION: Patients were randomised (1:1) to celecoxib 200mg twice daily or placebo for 2 yr. Patients with intermediate-risk NMIBC were recommended to receive six weekly mitomycin C instillations; high-risk NMIBC cases received six weekly bacillus Calmette-Guérin and maintenance therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was time to disease recurrence. Analysis was by intention to treat. RESULTS AND LIMITATIONS: A total of 472 patients were randomised (236:236). With median follow-up of 44 mo (interquartile range: 36-57), 3-yr recurrence-free rate (95% confidence interval) was as follows: celecoxib 68% (61-74%) versus placebo 64% (57-70%; hazard ratio [HR] 0.82 [0.60-1.12], p=0.2). There was no difference in high-risk (HR 0.77 [0.52-1.15], p=0.2) or intermediate-risk (HR 0.90 [0.55-1.48], p=0.7) NMIBC. Subgroup analysis suggested that time to recurrence was longer in pT1 NMIBC patients treated with celecoxib compared with those receiving placebo (HR 0.53 [0.30-0.94], interaction test p=0.04). The 3-yr progression rates in high-risk patients were low: 10% (6.5-17%) and 9.7% (6.0-15%) in celecoxib and placebo arms, respectively. Incidence of serious cardiovascular events was higher in celecoxib (5.2%) than in placebo (1.7%) group (difference +3.4% [-0.3% to 7.2%], p=0.07). CONCLUSIONS: BOXIT did not show that celecoxib reduces the risk of recurrence in intermediate- or high-risk NMIBC, although celecoxib was associated with delayed time to recurrence in pT1 NMIBC patients. The increased risk of cardiovascular events does not support the use of celecoxib. PATIENT SUMMARY: Celecoxib was not shown to reduce the risk of recurrence in intermediate- or high-risk non-muscle-invasive bladder cancer (NMIBC), although celecoxib was associated with delayed time to recurrence in pT1 NMIBC patients. The increased risk of cardiovascular events does not support the use of celecoxib.

Post-prostatectomy Lymphocoele Presenting With Renal Failure.

Since its advent in 2001, robotic-assisted laparoscopic prostatectomy has become the gold standard treatment for the management of localized prostate cancer. Pelvic lymphocoele is most commonly found after gynecological or renal transplant surgery or following extensive pelvic lymphadenectomy. Its formation following prostatectomy is not uncommon1 but it seldom causes major complications or morbidity.2 We present a case of a 66-year-old man who presented with left-sided abdominal pain, a palpable infra-umbilical mass, and renal failure. He was initially presumed to have high pressure chronic retention however catheterization did not result in any improvement in his renal function. Further investigations revealed a large lymphocoele causing bilateral ureteric obstruction with resultant hydronephrosis.

The future of financing for HIV services in Uganda and the wider sub-Saharan Africa region: should we ask patients to contribute to the cost of their care?

Whilst multi-lateral funding for HIV/AIDS dramatically increased from 2004 to 2008, it has largely plateaued in the last 8 years. Across sub-Saharan Africa, up to 20 % of total spending on health is used for HIV services, and of this over 85 % is estimated to come from international funding rather than in-country sources. In Uganda, the fiscal liability to maintain services for all those who are currently receiving it is estimated to be as much as 3 % of Gross Domestic Product (GDP). In order to meet the growing need of increased patient numbers and further ART coverage the projected costs of comprehensive HIV care and treatment services will increase substantially. Current access to HIV care includes free at point of delivery (provided by Ministry of Health clinics), as well as out-of-pocket financing and health insurance provided care at private for- and not for- profit facilities. The HIV response is funded through Ugandan Ministry of Health national budget allocations, as well as multilateral donations such as the President's Emergency Plan for AIDS in Africa (PEPFAR) and Global Fund (GF) and other international funders. We are concerned that current funding mechanism for HIV programs in Uganda may be difficult to sustain and as service providers we are keen to explore ways in which provide lifelong HIV care to as many people living with HIV (PLHIV) as possible. Until such time as the Ugandan economy can support universal, state-supported, comprehensive healthcare, bridging alternatives must be considered. We suggest that offering patients with the sufficient means to assume some of the financial burden for their care in return for more convenient services could be one component of increasing coverage and sustaining services for those living with HIV.

Embryology and adult urology - Not always mutually exclusive: A case report on true hermaphroditism at an adult urology clinic.

True hermaphrodite (TH) is one of the rarest varieties of disorders of sexual differentiation. Most patients present early in the life and are managed by pediatricians. We present a rare case of an adult TH which was first diagnosed by a urologist. We discuss the pathology of TH and its clinical relevance. Knowledge and awareness of embryology are vital to all specialties.

A rare case of testicular metastasis of bladder transitional cell carcinoma.

Metastases from bladder transitional cell carcinoma (TCC) to the testis are very rare. These are usually found on autopsy and occur in advanced or metastatic bladder cancers. More common, known primary tumors that metastasize to the testis include prostate, lungs, melanoma, gastro-intestinal tract and the kidney. We report a rare case of solitary and synchronous metastatic TCC of the bladder to the testis, discovered on histological examination. This case illustrates that metastatic neoplasm to uncommon sites should be considered in the differential diagnosis for patients with a history of advanced bladder TCC.

Acute urinary retention in women due to urethral calculi: A rare case.

We present a case of a 51-year-old woman with acute urinary retention caused by a urethral calculus. Urethral calculi in women are extremely rare and are usually formed in association with underlying genitourinary pathology. In this case, however, no pathology was detected via thorough urological evaluation. We discuss the pathogenesis, clinical presentation and treatment of urethral calculi. To our knowledge, this is the second reported case of a primary urethral calculus in a female with an anatomically normal urinary tract and the first in a middle-aged Caucasian female.

Diethylstilboestrol for the treatment of prostate cancer: past, present and future.

The aim of this review was to discuss the most recent data from current trials of diethylstilboestrol (DES) to identify its present role in advanced prostate cancer treatment as new hormonal therapies emerge. The most relevant clinical studies using DES in castration-refractory prostate cancer (CRPC) were identified from the literature. The safety, efficacy, outcomes and mechanisms of action are summarized. In the age of chemotherapy this review highlights the efficacy of oestrogen therapy in CRPC. The optimal point in the therapeutic pathway at which DES should be prescribed remains to be established.

Bladder neck sparing in radical prostatectomy.

The role of a bladder neck sparing (BNS) technique in radical prostatectomy (RP) remains controversial. The potential advantages of improved functional recovery must be weighed against oncological outcomes. We performed a literature review to evaluate the current knowledge regarding oncological and functional outcomes of BNS and bladder neck reconstruction (BNr) in RP. A systematic literature review using on-line medical databases was performed. A total of 33 papers were identified evaluating the use of BNS in open, laparoscopic and robotic-assisted RP. The majority were retrospective case series, with only one prospective, randomised, blinded study identified. The majority of papers reported no significant difference in oncological outcomes using a BNS or BNr technique, regardless of the surgical technique employed. Quoted positive surgical margin rates ranged from 6% to 32%. Early urinary continence (UC) rates were ranged from 36% to 100% at 1 month, with long-term UC rate reported at 84-100% at 12 months if the bladder neck (BN) was spared. BNS has been shown to improve early return of UC and long-term UC without compromising oncological outcomes. Anastomotic stricture rate is also lower when using a BNS technique.

Developing independent investigators for clinical research relevant for Africa.

Sustainable research capacity building requires training individuals at multiple levels within a supportive institutional infrastructure to develop a critical mass of independent researchers. At many African medical institutions, a PhD is important for academic promotion and is, therefore, an important focal area for capacity building programs. We examine the training at the Infectious Diseases Institute (IDI) as a model for in-country training based on systems capacity building and attention to the academic environment. PhD training in Africa should provide a strong research foundation for individuals to perform independent, original research and to mentor others. Training the next generation of researchers within excellent indigenous academic centers of excellence with strong institutional infrastructure will empower trainees to ask regionally relevant research questions that will benefit Africans.

Early prostate cancer--which treatment do men prefer and why?

STUDY TYPE: Preference (prospective cohort). LEVEL OF EVIDENCE: 1b. What's known on the subject? and What does the study add? In general the literature suggests that there is a need for improvement in aiding men diagnosed with early prostate cancer in their decision making about treatment options and that our understanding of this process is inadequate. There is limited data analyzing the reasons why these men decide between potentially curative or observational treatments and data evaluating patients' views before and after definitive therapy are scarce. This study begins the process of understanding the reasons underlying a patient's final treatment decision. Being a prospective study, it looks at the thought processes of these men before treatment during the time the decision is made. It also documents how satisfied patients are with their choice after their treatment and whether they would choose the same treatment again. OBJECTIVE: To identify the reasons for patients with localised prostate cancer choosing between treatments and the relationship of procedure type to patient satisfaction post-treatment. PATIENTS AND METHODS: 768 men with prostate cancer (stage T1/2, Gleason≤7, PSA<20 ug/L) chose between four treatments: radical prostatectomy, brachytherapy, conformal radiotherapy and active surveillance. Prior to choosing, patients were counselled by a urological surgeon, clinical (radiation) oncologist and uro-oncology specialist nurse. Pre-treatment reasons for choice were recorded. Post-treatment satisfaction was examined via postal questionnaire. RESULTS: Of the 768 patients, 305 (40%) chose surgery, 237 (31%) conformal beam radiotherapy, 165 (21%) brachytherapy and 61 (8%) active surveillance. Sixty percent of men who opted for radical prostatectomy were motivated by the need for physical removal of the cancer. Conformal radiotherapy was mainly chosen by patients who feared other treatments (n=63, 27%). Most men chose brachytherapy because it was more convenient for their lifestyle (n=64, 39%). Active surveillance was chosen by patients for more varied reasons. Post-treatment satisfaction was assessed in a subgroup who took part in the QOL aspect of this study. Of the respondents to the questionnaire, 212(87.6%) stated that they were satisfied/extremely satisfied with their choice and 171(92.9%) indicated they would choose the same treatment again. CONCLUSION: Men with early prostate cancer have clear reasons for making decisions about treatment. Overall, patients were satisfied with the treatment and indicated that despite different reasons for choosing treatment, they would make the same choice again.

The '2-week wait' rule for referrals for suspected urological cancers--urgent need for refinement of criteria.

INTRODUCTION: All NHS-suspected cancers should be seen within 2 weeks of referral and are referred under government guidelines (Health Service Circular 205; HSC 205). This policy will be subject to review in 2009. Review is vital to allow the appropriate detection of malignancy without overburdening the premium clinic slots with the healthy. PATIENTS AND METHODS: A total of 170 consecutive patients were referred from January-June 2005. Referral details, patient information, events and time to diagnosis were recorded. RESULTS: Of these 170 patients, 143 were suitable for analysis. Forty-three patients (30%) were referred with frank haematuria, of whom 30% had bladder cancer. Nine percent of patients (n = 13) had microscopic haematuria none of whom had cancer. A quarter of the patients (n = 35) were referred with suspected testis cancer but none had cancer. Forty-one patients were referred with serum prostate-specific antigen (PSA) elevation; 18 cancers were detected in this group. Ten men had PSA values greater than 50 ng/ml. Only two cancers were suitable for radical prostatectomy. No cancer was found in patients less than 50 years of age. CONCLUSIONS: A high cancer incidence was found (27.9%), the majority of which was bladder cancer or advanced prostate cancer. Out of the 143 patients, no malignancy was diagnosed in any patient less than 50 years of age, no malignancy was diagnosed in any of the microscopic haematuria group and there was no cancer diagnosed in the group of patients referred with scrotal swellings. We suggest that some guidelines are leading to referral of patients with low cancer risk. When the HSC 205 is revised in 2009, we hope studies such as ours are taken into consideration in order to improve resource utilisation.

Adenocarcinoma of the caecum metastatic to the bladder: an unusual cause of haematuria.

BACKGROUND: Primary malignancies of colorectal origin can metastasise to the bladder. Reports are however extremely rare, particularly from the caecum. CASE REPORT: The report describes the case of a 45-year old male with Duke's B caecal carcinoma treated with a laparoscopically-assisted right hemicolectomy and adjuvant 5-Fluorouracil chemotherapy. Subsequently, a metastatic lesion to the bladder was demonstrated and successfully excised by partial cystectomy. CONCLUSION: In order that optimal therapeutic options can be determined, it is important for clinicians to distinguish between primary disease of the bladder and other causes of haematuria. Various immunohistochemical techniques attempt to differentiate primary adenocarcinoma of the bladder from secondary colorectal adenocarcinoma. Suspicion of metastatic disease must be raised when histologically unusual bladder tumours are identified.

Bilateral testicular metastases from prostatic carcinoma.

Testicular metastasis from carcinoma of the prostate is rare. We report a case of carcinoma of the prostate with bilateral testicular metastases 7 years after the initial diagnosis. The exact prognosis is not known but it usually indicates advanced disease. Although testicular metastasis is uncommon, it should be considered when a patient presents with a lump in the testis, particularly in a patient known to have another primary malignancy.

Iatrogenic iodine as a cause of hypothyroidism in infants with end-stage renal failure.

Between 1996 and 2005, two of seven infants in our unit on overnight continuous-cycle peritoneal dialysis (CCPD) acquired hypothyroidism following normal thyroid function on neonatal screening. Case 1 had posterior urethral valves, commenced CCPD at day 29, and developed hypothyroidism requiring treatment at 3 months: TSH 258 micro/l (ref.: 0.3-3.8), total thyroxine 74 nmol/l (ref.: 77-159). Plasma iodine concentration was 7.44 micromol/l (ref.: 0.23-0.68). Iodine concentrations in peritoneal dialysis (PD) fluid were found to be higher at the end of the first cycle (11.4 micromol/l) than at the end of the twelfth cycle (1.55 micromol/l). Case 2 had posterior urethral valves, commenced CCPD on day 4 and was diagnosed with hypothyroidism following a prolonged jaundice screen. Thyroxine replacement was stopped 2 months after a renal transplant. A third child commenced CCPD on day 2 and had high plasma iodine concentrations at 8 weeks (5.79 micromol/l). He had borderline thyroid function, not requiring replacement. Our hypothesis is that these infants developed hypothyroidism as a consequence of iodine exposure via the Wolff-Chaikoff effect. Iodine levels were higher in the PD fluid than in plasma. This suggests that povidine-iodine 10% in the PD cap may be the source of the high plasma iodine levels.

Troponin T and N-terminal pro-brain natriuretic peptide changes in patients undergoing transurethral resection of the prostate.

PURPOSE: We investigated whether transurethral resection of the prostate (TURP) caused subclinical myocardial damage or cardiac dysfunction by measuring troponin T (Trop T) and N-terminal pro-brain natriuretic peptide (pro-BNP). MATERIALS AND METHODS: A total of 52 consenting patients took part in this study. All had a detailed medical history including cardiac history taken. On the day of the operation all patients had troponin T, pro-BNP, full blood count and urea, electrolytes and creatinine measured preoperatively. A preoperative and postoperative electrocardiogram was performed. Patients in renal failure were excluded from analysis. During the operations factors such as blood loss, operative time, tissue resected and fluid absorption were monitored. On postoperative day 1 all the previously mentioned tests were repeated. RESULTS: Mean patient age was 71 years (range 52 to 85). Eight patients had a history of associated cardiac problems. Mean preoperative and postoperative hemoglobin were 14.1 gm/dl (range 10.5 to 17) and 13.3 gm/dl (range 9.9 to 16.2), respectively. None of the patients had significant (greater than 1,000 ml) fluid absorption during TURP, which was calculated using ethanol tagged glycine. Mean blood loss measured with a photometer was 129.7 ml (range 0 to 1,800). Mean operative time was 28.4 minutes (range 5 to 50) and mean weight of prostatic tissue resected was 15.2 gm (range 1 to 47). Preoperative Trop T was less than 0.01 mcg/ml in all patients and mean pro-BNP was 39.2 pg/ml (range 0.5 to 866). Postoperative Trop T was less than 0.01 mcg/ml in all but 1 patient who experienced chest pain after TURP and had an increased Trop T (0.28 mcg/ml). Mean postoperative pro-BNP was 54.57 pg/ml (range 1 to 679). A total of 37 patients had an increase in pro-BNP which was still within the reference range for the age group. There were no significant electrocardiogram changes postoperatively. The Trop T changes were not statistically significant (Wilcoxon sign ranked test p = 0.31) although they may be clinically significant. CONCLUSIONS: Our study indicates that in patients with no prior cardiac history TURP does not cause myocardial damage indicated by nonincrease of Trop T. There are slight increases in pro-BNP after TURP in some patients although the exact clinical significance is uncertain.

Systemic capacity building: a hierarchy of needs.

'Capacity building' is the objective of many development programmes and a component of most others. However, satisfactory definitions continue to elude us, and it is widely suspected of being too broad a concept to be useful. Too often it becomes merely a euphemism referring to little more than training. This paper argues that it is more important to address systemic capacity building, identifying a pyramid of nine separate but interdependent components. These form a four-tier hierarchy of capacity building needs: (1) structures, systems and roles, (2) staff and facilities, (3) skills, and (4) tools. Emphasizing systemic capacity building would improve diagnosis of sectoral shortcomings in specific locations, improve project/programme design and monitoring, and lead to more effective use of resources. Based on extensive action research in 25 States, experience from India is presented to illustrate how the concept of the capacity building pyramid has been put to practical use.