Clinical trials in metastatic prostate cancer – Has there been real progress in the past decade?

Hormone refractory prostate cancer remains a challenge. While only palliative treatment strategies were available for the past several decades, many promising agents have been investigated over the past decade. Of those the taxanes appeared with significant anti-tumor activity and recently, two large randomized controlled trials demonstrated for the first time, a survival and palliative benefit with docetaxel based chemotherapy. In the current era, recurrent disease after local treatment for localized disease is diagnosed long before evidence of systemic disease. With earlier institution of hormonal treatments, patients are becoming "hormone refractory" earlier in the course of their disease with considerable long life expectancy. Hence, there is a greater need than ever for more treatment options for this expanding group of patients. A number of new systemic therapies have recently emerged, based on a deeper understanding of prostate cancer biology. Novel chemotherapeutics such as the epothilones, molecularly targeted therapies against angiogenesis, the proteosome and endothelin receptor antagonists, as well as biological agents such as anti-sense oligonucleotides are being tested as part of the armamentarium. Key to progress in the therapy of this fatal disease is the commitment and timely enrolment of prostate cancer patients in clinical trials.     

Buccal mucosal urethroplasty: a versatile technique for all urethral segments

OBJECTIVE: To present our experience with buccal mucosa urethroplasty for substitution of all segments of the anterior urethra, as the buccal mucosal graft (BMG) has emerged as the tissue of choice for single-stage reconstruction of bulbar urethral strictures, but its use for reconstructing meatal, pendulous and pan-urethral strictures has not been widely reported. PATIENTS AND METHODS: Between January 1998 and October 2003, 92 patients had a BMG substitution urethroplasty at our institution; 75 had a single-stage dorsal onlay BMG urethroplasty (bulbar 41, pendulous 16 and pan-urethral 18; six combined penile skin flap and BMG) and 17 (pendulous five, pan-urethral 10, bulbar two) a two-stage urethroplasty. Recurrence rates, complications and cosmetic outcomes were analysed retrospectively. RESULTS: Over a median (range) follow-up of 34 (8-72) months, 66 (88%) patients with a one-stage reconstruction (14/16 pendulous; 37/41, 90%, bulbar; 15/16 pan-urethral) remained stricture-free. The mean (range) time to recurrence was 9.4 (3-17) months. Of the nine recurrent strictures, six were managed by one-stage optical urethrotomy and three required a repeat urethroplasty. In patients who had a staged procedure, after a mean follow-up of 24.2 (9-56) months, one had complete graft loss, requiring re-grafting, five required stomal revision after stage 1, and only two (12%) developed a recurrent stricture after the two-stage urethroplasty. CONCLUSION: A one-stage dorsal onlay BMG urethroplasty provides excellent results for strictures involving any segment of the anterior urethra. The BMG appears to be the most versatile urethral substitute, as it can be successfully used for both one- and two-stage reconstruction of the entire anterior urethra.     

Use of multiple opportunities for improving feeding practices in under-twos within child health programmes

Objectives: In a community randomized trial, we aimed to promoteexclusive breastfeeding and appropriate complementary feedingpractices in under-twos to ascertain the feasibility of usingavailable channels for nutrition counselling, their relativeperformance and the relationship between intensity of counsellingand behaviour change. We also assessed whether using multipleopportunities to impart nutrition education adversely affectedroutine activities. Methods: We conducted a community randomized, controlled effectivenesstrial in rural Haryana, India, with four intervention and fourcontrol communities. We trained health and nutrition workersin the intervention communities to counsel mothers at multiplecontacts on breastfeeding exclusively for 6 months and on appropriatecomplementary feeding practices thereafter. The interventionwas not just training health and nutrition workers in counsellingbut included community and health worker mobilization. Findings: In the intervention group, about 32% of caregiverswere counselled by traditional birth attendants at birth. Themost frequent sources of counselling from birth to 3 monthswere immunization sessions (45.1%) and home visits (32.1%),followed closely by weighing sessions (25.5%); from 7 to 12months, home visits (42.6%) became more important than the othertwo. An increase in the number of channels through which caregiverswere counselled was positively associated with exclusive breastfeedingprevalence at 3 months (p = 0.002), consumption of milk/cerealgruel or mix use at 9 months (p = 0.004) and 18 months (p =0.003), undiluted milk at 9 months (p<0.0001) and 24 hournon-breast-milk energy intakes at 18 months (p = 0.023), aftercontrolling for potential confounding factors. Interventionareas, compared with the control, had higher coverage for vitaminA (45% vs. 11.5%) and iron folic acid (45% vs. 0.4%) supplementation. Conclusions: Using multiple available opportunities and workersfor counselling caregivers was feasible, resulted in high coverageand impact, and instead of disrupting ongoing services, resultedin their improvement.     

Racial disparities in outcomes of inpatient stroke rehabilitation

OBJECTIVE: To determine whether race is associated with outcomes of inpatient stroke rehabilitation. DESIGN: Retrospective cohort study. SETTING: A community-based inpatient rehabilitation facility. PARTICIPANTS: Poststroke patients (N=1002) admitted to a community-based inpatient rehabilitation facility between 1995 and 2001. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Functional improvement at discharge from the rehabilitation facility, discharge disposition, and functional improvement at 3 months after discharge. Inpatient and follow-up data were collected from the facility's electronic patient database. We used the FIM instrument to assess functional status at admission, discharge, and follow-up. RESULTS: In multivariable models, blacks achieved less functional improvement at discharge (-1.9 FIM points, P=.02) compared with whites and, despite worse FIM scores, were more likely to be discharged to home (adjusted odds ratio=1.7; 95% confidence interval, 1.1-2.5). Although Asian-American patients did not differ from whites in terms of functional improvement at discharge or disposition, they had less improvement at 3 months following discharge (-6.3 FIM points, P=.005). CONCLUSIONS: We identified racial disparities in poststroke outcomes in a community-based inpatient rehabilitation facility. Future research in stroke rehabilitation should explore the consistency of these findings across settings and if they are confirmed, identify explanatory mediators to better inform efforts to eliminate racial disparities.     

Transvaginal inversion of urinary bladder after concealment of box in vagina

A case of massive transvaginal inversion of urinary bladder through a large vesicovaginal fistula is reported. It was the outcome of concealing a metal box in the vagina for a period of six months. The inversion was reduced and the defect repaired through a vaginal route, with complete functional and anatomic restoration of the urinary tract.     

Health-related quality of life following operative treatment of unstable ankle fractures: a prospective observational study

BACKGROUND: Although Weber type B ankle fractures are often considered benign with a good prognosis, evidence from observational studies suggests that 17% to 24% of such patients may have less satisfactory outcomes. Although the explanation for variability in outcomes remains unclear, previous studies of other surgical procedures have suggested nonsurgery-related causes account for much of the variability in outcomes. METHODS: We conducted a prospective observational cohort study to evaluate health-related quality of life in 30 patients with unstable ankle fractures who were otherwise healthy. Only patients from 2 university-affiliated hospitals sustaining unstable type B Weber injury patterns requiring surgery were eligible. Patients provided detailed baseline information regarding alcohol consumption, smoking habits, and educational level. Patients completed the short form 36 questionnaire and a visual analogue pain scale at regular follow-up intervals. RESULTS: The average patient age was 51.6 years (SD 15.2 years), and 57% (17 out of 30) were male. The majority of fractures were the result of a fall (67%, 20 out of 30), and all were closed injuries. Almost half of all patients were smokers (47%, 14 out of 30), whereas 43% consumed alcohol on a weekly basis (13 out of 30). Forty-three percent of patients (13 out of 30) had obtained an elementary or high school level of education. Patients experienced significant improvements in all domains of the SF-36 questionnaire (P < 0.001), except general health, which remained essentially normal over the 24-month period. Study patients achieved scores similar to age-matched U.S. normative data across 6 of the 8 domains (Role Emotional, Social Function, Mental Health, Bodily Pain, Vitality, and General Health). However, patients' physical function and role physical scores remained significantly lower than US norms at 24 months (21.8 and 20.7 points lower on a 100-point scale, respectively; P < 0.001). Smoking history (P = 0.02), presence of a medial malleolar fracture (P = 0.02), and lower levels of education (P = 0.01) were significant independent predictors of lower physical function up to 3 months postoperation. Lower mental health domain scores were significantly associated with alcohol use (P = 0.02) and increasing age (P = 0.04). CONCLUSIONS: As is the case in many other areas, social factors may be important determinants of outcome in patients with traumatic fractures. Optimal orthopedic care may involve attention to modifiable risk factors, including smoking and alcohol consumption.