C.E.R.A. maintains stable hemoglobin in Latin American patients on dialysis

Background

C.E.R.A. is a continuous erythropoietin receptor activator with characteristics that permit a once-monthly schedule of administration for the maintenance treatment for chronic kidney disease (CKD) patients. The main objective of this study was to assess the maintenance of Hb concentration with once-monthly intravenous and/or subcutaneous C.E.R.A. therapy in Latin American dialysis patients with chronic renal anemia previously treated with epoetin alfa s.c or i.v 1–3 times per week.

Methods

This was a single-arm, open-label, multicenter, 32-week study of anemic patients with CKD previously treated with epoetin alfa sc or iv 1–3 times per week. After a 4-week screening period, during which mean Hb levels were maintained between 10.5 and 12.5 g/dL on their previous erythropoiesis stimulating agent, eligible patients entered a 16-week C.E.R.A. dose titration period followed by a 4-week efficacy evaluation period (EEP) and a 28-week safety follow-up. The starting dose of C.E.R.A. was based on the previous dose of epoetin alfa. Doses of C.E.R.A. were then adjusted to maintain Hb levels within ±1.0 g/dL of the reference concentration and between 10.5 and 12.5 g/dL. The Hb reference concentration was defined as the mean of all Hb levels during screening. The primary end point was the proportion of patients maintaining a mean Hb concentration (g/dL) within ±1 g/dL of their reference Hb and between 10.5 and 12.5 g/dL during the EEP.

Results

A total of 163 patients from 27 centers in Argentina, Brazil, Chile, Colombia, Ecuador, Mexico, Peru, Uruguay, and Venezuela entered the treatment period and 102 completed the prescribed course of C.E.R.A. Forty-five patients (43.7 %) maintained a mean Hb concentration within ±1 g/dL of their reference Hb value and between 10.5 and 12.5 g/dL during the EEP. The median monthly dose remained constant at 120 μg during the titration period and during the EEP. On the average, there were only 2.3 dose changes per patient in 28 weeks of treatment, covering 7 C.E.R.A. scheduled administrations. 53 % of all dose changes were dose decreases, 47 % increases. A total of 10 AEs and 4 SAEs were considered to be related to the study treatment.

Conclusions

Once-monthly C.E.R.A. treatment effectively maintains stable Hb concentrations in patients with chronic renal anemia undergoing dialysis with a good safety and tolerability profile.     

Obesity and Prostate Cancer: Weighing the Evidence

Context

Obesity and prostate cancer (PCa) affect substantial proportions of Western society. Mounting evidence, both epidemiologic and mechanistic, for an association between the two is of public health interest. An improved understanding of the role of this modifiable risk factor in PCa etiology is imperative to optimize screening, treatment, and prevention.

Objective

To consolidate and evaluate the evidence for an epidemiologic link between obesity and PCa, in addition to examining the proposed underlying molecular mechanisms.

Evidence acquisition

A PubMed search for relevant articles published between 1991 and July 2012 was performed by combining the following terms: obesity, BMI, body mass index and prostate cancer risk, prostate cancer incidence, prostate cancer mortality, radical prostatectomy, androgen-deprivation therapy, external-beam radiation, brachytherapy, prostate cancer and quality of life, prostate cancer and active surveillance, in addition to obesity, BMI, body mass index and prostate cancer and insulin, insulin-like growth factor, androgen, estradiol, leptin, adiponectin, and IL-6. Articles were selected based on content, date of publication, and relevancy, and their references were also searched for relevant articles.

Evidence synthesis

Increasing evidence suggests obesity is associated with elevated incidence of aggressive PCa, increased risk of biochemical failure following radical prostatectomy and external-beam radiotherapy, higher frequency of complications following androgen-deprivation therapy, and increased PCa-specific mortality, although perhaps a lower overall PCa incidence. These results may in part relate to difficulties in detecting and treating obese men. However, multiple molecular mechanisms could explain these associations as well. Weight loss slows PCa in animal models but has yet to be fully tested in human trials.

Conclusions

Obesity appears to be linked with aggressive PCa. We suggest clinical tips to better diagnose and treat obese men with PCa. Whether reversing obesity slows PCa growth is currently unknown, although it is an active area of research.     

Effect of Diabetes on Outcomes in Patients Undergoing Emergent Cholecystectomy for Acute Cholecystitis

Background

The purpose of the present study was to determine the prevalence of diabetes and its effect on surgical outcomes in patients undergoing emergent, in-patient cholecystectomy for acute cholecystitis. Some 8.3 % of the U.S. population has diabetes and this number is projected to rise to 21–33 % by 2050. Diabetes is considered to be associated with a higher incidence of acute cholecystitis; however, its impact on outcomes is unknown.

Methods

The American College of Surgeons National Surgical Quality Improvement Program database was queried to identify all patients with acute cholecystitis who underwent emergent in-patient cholecystectomy from 2004 to 2010. The study population was divided into two groups: diabetics and non-diabetics. Diabetics were further subdivided into those taking oral medication and those on insulin. Demographics, co-morbidities, and wound classification were compared with univariate analysis, and 30-day outcomes were compared with univariate and multivariate analyses.

Results

A total of 5,460 patients met the inclusion criteria. Of these 770 (14.10 %) had a diagnosis of diabetes. Mortality was higher for diabetics than for non-diabetics [4.4 vs 1.4 %, adjusted odds ratio (AOR) (95 % CI): 1.79 (1.09, 2.94), adj-p = 0.022]. Preoperative perforation rates were 25.1 and 13.0 %, respectively [AOR (95 % CI): 1.34 (1.09, 1.65), adj-p = 0.005]. The adjusted risk of cardiovascular events and renal failure was significantly higher for diabetics. Insulin treatment, but not oral medication, was associated with a significant increase in mortality, preoperative perforation, superficial surgical site infection, septic shock, cardiovascular incidents, and renal insufficiency.

Conclusions

In patients undergoing cholecystectomy for acute cholecystitis, diabetes increases the risk of mortality, cardiovascular events, and renal failure. Insulin-treated diabetics have more co-morbidities and poorer outcomes.     

Incidence and Consequence of Close Margins in Patients with Ductal Carcinoma-In Situ Treated with Mastectomy: Is Further Therapy Warranted?

Background

The impact of close margins in patients with ductal carcinoma-in situ (DCIS) treated with mastectomy is unclear; however, this finding may lead to a recommendation for postmastectomy radiotherapy (PMRT). We sought to determine the incidence and consequences of close margins in patients with DCIS treated with mastectomy.

Methods

The records of 810 patients with DCIS treated with mastectomy from 1996 through 2009 were reviewed. Clinical and pathologic factors were analyzed with respect to final margin status. Median follow-up was 6.3 years.

Results

Overall, 94 patients (11.7 %) had close margins (positive, n = 5; negative but ≤1 mm, n = 54; 1.1–2.9 mm, n = 35). Independent risk factors for close margins included multicentricity, pathologic lesion size ≥1.5 cm, and necrosis, but not age, use of skin-sparing mastectomy, or immediate reconstruction (p > 0.05). Seven patients received PMRT, and none had a locoregional recurrence (LRR). Among the remaining 803 patients, the 10-year LRR rate was 1 % (5.0 % for margins ≤1 mm, 3.6 % for margins 1.1–2.9 mm, and 0.7 % for margins ≥3 mm [p < 0.001]). The 10-year rate of contralateral breast cancer was 6.4 %. On multivariate analysis, close margins was the only independent predictor of LRR (p = 0.005).

Conclusions

Close margins occur in a minority of patients undergoing mastectomy for DCIS and is the only independent risk factor for LRR. As the LRR rate in patients with close margins is low and less than the rate of contralateral breast cancer, PMRT is not warranted except for patients with multiple close/positive margins that cannot be surgically excised.     

Factors influencing the acquisition of Stenotrophomonas maltophilia infection in cystic fibrosis patients

BackgroundStenotrophomonas maltophilia is one of the most common multi-drug resistant organisms causing pulmonary infections in CF patients. It is unknown whether S. maltophilia infection follows the same pattern and shares similar risk factors for acquisition as described for Pseudomonas aeruginosa.MethodsWe examined all clinical events from 1997 to 2008 in the Toronto CF Database to identify risk factors for the acquisition of S. maltophilia and to define distinct patterns of infection.ResultsWe followed 601 patients over 12 years, during which time one quarter of subjects had at least one positive culture for S. maltophilia; the incidence rate was slightly higher in children (11.6/100 person years) compared with adults (10.6/100 person years). Using multi-variable Cox proportional hazards models, steeper rate of FEV₁ decline was a significant risk factor for S. maltophilia acquisition, whereas new infections were less likely to occur with greater oral antibiotic use and a history of Burkholderia cepacia complex infection.ConclusionsThis study illustrates the evolution of S. maltophilia infection over time in a large cohort of adults and children with CF. Younger CF patients, and those with greater lung function decline were at increased risk of S. maltophilia infection. The use of oral antibiotics to maintain lung function may be a way of decreasing the risk of infection. However, the optimal management of CF patients with persistent S. maltophilia infection is not yet known and requires further studies.     

Applications of complementary therapies during rehabilitation for individuals with traumatic Spinal Cord Injury: Findings from the SCIRehab Project

Objective: Evaluate the use of complementary therapies during rehabilitation for patients with traumatic spinal cord injury (SCI).

Design: Secondary analyses were conducted to identify the use and associated outcomes of complementary therapies provided by occupational therapists (OTs) and physical therapists (PTs) during rehabilitation from a public dataset.

Setting: Inpatient rehabilitation.

Participants: A public dataset composed of 1376 patients with SCI that were enrolled in a five-year, multi-center investigation, the SCIRehab Project. Secondary analyses focused on a subset of 93 patients (47 who received complementary therapy during treatment and 46 case-matched controls who received no complementary therapy).

Interventions: OTs and PTs recorded use of complementary therapies during sessions, including yoga, Pilates, tai chi, aromatherapy, relaxation techniques, imagery and other.

Outcome Measures: Pain interference, pain severity, mobility, and social integration.

Results: Three percent of participants received any complementary therapies. Patients who received complementary therapies showed greater reductions in pain severity from 6 months to 12 months relative to matched controls. Furthermore, the amount of time that patients received complementary therapies during physical therapy sessions was associated with reduced pain interference at 6 months and with reduced pain severity at the 6-month and 12-month follow-ups. Complementary therapy use was not associated with mobility or social integration.

Conclusion: The current study provides preliminary evidence documenting the limited use of complementary therapies in rehabilitation settings and highlights the opportunity for further research, particularly regarding pain-related outcomes.