Restoring arteriovenous access: Pilot study using a scoring balloon in 50 patients.

BACKGROUND: Arteriovenous access failure is most often due to the development of neointimal hyperplastic stenoses. Balloon angioplasty remains standard of care for endovascular treatment of stenoses obstructing blood flow in hemodialysis fistulas and grafts. Scoring balloon technologies have been developed to disrupt the atheromatous plaque and have shown to be safe and effective for treating stenosis in the hemodialysis access circuit. However, improvement in patency has yet to be established. METHODS: This prospective, single-arm study included 50 patients with stenosed hemodialysis fistula/grafts treated with the AngioSculpt® scoring balloon (Philips) and followed for 6 months. The primary endpoint was target lesion primary patency at 2 and 6 months defined as freedom from re-intervention. RESULTS: Treatment with the scoring balloon resulted in a reduction in stenosis from 78% ± 13.36% to 7.2% ± 7.57% (mean ± standard deviation). Scoring balloon inflation pressures averaged 11.4 atm; no slippage/dissections occurred. After 2 months, 10% of patients required re-intervention. At 6 months, 19% of patients required re-intervention. The 6-month freedom from re-intervention rate was higher for patients with stenosed fistulas (83.3%) compared to patients with stenosed grafts (71.4%). Six-month patency rates were highest for patients with no or one previous intervention (91.6% and 90.0%, respectively); patients with two to five preceding interventions had a 6-month patency rate of 80%, and those with more than five previous interventions had a 50% 6-month patency rate. CONCLUSION: Results from this pilot study suggest that the AngioSculpt scoring balloon may be a viable treatment option for stenosed arteriovenous fistula/graft access.

Hg concentrations in fish from coastal waters of California and Western North America.

The State of California conducted an extensive and systematic survey of mercury (Hg) in fish from the California coast in 2009 and 2010. The California survey sampled 3483 fish representing 46 species at 68 locations, and demonstrated that methylHg in fish presents a widespread exposure risk to fish consumers. Most of the locations sampled (37 of 68) had a species with an average concentration above 0.3µg/gwet weight (ww), and 10 locations an average above 1.0µg/gww. The recent and robust dataset from California provided a basis for a broader examination of spatial and temporal patterns in fish Hg in coastal waters of Western North America. There is a striking lack of data in publicly accessible databases on Hg and other contaminants in coastal fish. An assessment of the raw data from these databases suggested the presence of relatively high concentrations along the California coast and in Puget Sound, and relatively low concentrations along the coasts of Alaska and Oregon, and the outer coast of Washington. The dataset suggests that Hg concentrations of public health concern can be observed at any location on the coast of Western North America where long-lived predator species are sampled. Output from a linear mixed-effects model resembled the spatial pattern observed for the raw data and suggested, based on the limited dataset, a lack of trend in fish Hg over the nearly 30-year period covered by the dataset. Expanded and continued monitoring, accompanied by rigorous data management procedures, would be of great value in characterizing methylHg exposure, and tracking changes in contamination of coastal fish in response to possible increases in atmospheric Hg emissions in Asia, climate change, and terrestrial Hg control efforts in coastal watersheds.

A unique variant of Poland-Mobius syndrome with dextrocardia and a 3q23 gain.

The combined Poland and Mobius syndrome occurs rarely and with a wide range of features. There is no consensus on the etiology of this syndrome; familial, sporadic cases and likely environmental insult cases have been reported. This sporadic case represents a unique variant in the spectrum of this syndrome.

Refeeding syndrome in very-low-birth-weight intrauterine growth-restricted neonates.

OBJECTIVE: Determine the incidence of refeeding syndrome, defined by the presence of hypophosphatemia in very-low-birth-weight (VLBW) infants with intrauterine growth restriction (IUGR) compared with those without IUGR. STUDY DESIGN: In this retrospective cohort study, VLBW infants admitted over a 10-year period (271 IUGR and 1982 non-IUGR) were evaluated for specific electrolyte abnormalities in the first postnatal week. RESULT: IUGR infants were significantly more likely to have hypophosphatemia (41% vs 8.9%, relative risk (95% confidence interval: 7.25 (5.45, 9.65)) and severe hypophosphatemia (11.4% vs 1%, 12.06 (6.82, 21.33)) in the first postnatal week. The incidence of hypophosphatemia was significantly associated with the presence of maternal preeclampsia in all VLBW infants (odds ratio (OR): 2.58 (1.96, 3.40)) when controlling for birth weight and gestational age. CONCLUSION: Refeeding syndrome occurs in VLBW infants with IUGR and born to mothers with preeclampsia. Close monitoring of electrolytes, especially phosphorus, is warranted in this population.

Opioid genetics: the key to personalized pain control?

There are now several strong opioids available to choose from for the relief of moderate to severe pain. On a population level, there is no difference in terms of analgesic efficacy or adverse reactions between these drugs; however, on an individual level there is marked variation in response to a given opioid. The genetic influences to this variation are complex, and although current research has shown some promising results, these have not been replicated across larger studies and as such the ultimate aim of personalized prescribing remains elusive. If personalized prescribing could be achieved this would have a major impact at an individual level to facilitate safe, effective and rapid symptom control. This review presents some of the recent positive advances in opioid pharmacogenetic studies, focusing on associations between candidate genes and the three main elements of opioid response: analgesic, upper gastrointestinal and central adverse reactions.

Multi-center experience of 164 consecutive Hemodialysis Reliable Outflow [HeRO] graft implants for hemodialysis treatment.

OBJECTIVE: To report a multi-center experience with the novel Hemodialysis Reliable Outflow (HeRO) vascular access graft. MATERIALS AND METHODS: Four centers conducted a retrospective review of end stage renal disease patients who received the HeRO device from implant to last available follow-up. Data is available on 164 patients with an accumulated 2092.1 HeRO implant months. RESULTS: At 6 months, HeRO primary and secondary patency is 60% and 90.8%, respectively and at 12 months, 48.8% and 90.8%, respectively. At 24 months, HeRO had a primary patency of 42.9% and secondary patency was 86.7%. Interventions to maintain or re-establish patency have been required in 71.3% of patients (117/164) resulting in an intervention rate of 1.5/year. Access related infections have been reported in 4.3% patients resulting in a rate of 0.14/1000 implant days. CONCLUSIONS: In our experience the HeRO device has performed comparably to standard AVGs and has proven superior to TDCs in terms of patency, intervention, and infection rates when compared to the peer-reviewed literature. As an alternative to catheter dependence as a means for hemodialysis access, this graft could reduce the morbidity and mortality associated with TDCs and have a profound impact on the costs associated with catheter related infections and interventions.

Diagnóstico de atresia de la arteria coronaria principal izquierda mediante tomografía computarizada volumétrica cardíaca de 320 detectores / Diagnosis of atresia of the main left coronary artery using 320-detector volumetric cardiac computed tompography

La ausencia congénita del tronco coronario izquierdo es una de las anomalías de arterias coronarias más raras. Presentamos un caso en el que se sospechó este diagnósticomediante angiografía coronaria, confirmándose mediantetomografíacomputarizada (TC) volumétricacardíaca adquirida en un solo latido (AU)

The congenital absence of the left coronary trunk is one of the rarest anomalies of the coronary artery. We present a case in which this anomaly was suspected at cardiac catheterization and confirmed at volumetric cardiac computed tomography (CT) with a single heart beat (AU)

[Diagnosis of atresia of the main left coronary artery using 320-detector volumetric cardiac computed tomography [corrected]]. / Diagnóstico de atresia de la arteria coronaria principal izquierda mediante tomografía computarizada volumétrica cardíaca de 320 detectores.

The congenital absence of the left coronary trunk is one of the rarest anomalies of the coronary artery. We present a case in which this anomaly was suspected at cardiac catheterization and confirmed at volumetric cardiac computed tomography (CT) with a single heart beat.

Evolving knowledge of opioid genetics in cancer pain.

Inter-individual variation in response to opioids for cancer pain is a well-established phenomenon. Variation occurs in the dose of opioid required, the analgesic efficacy of the opioid and also in the side-effects experienced by the individual taking the drug. To date, no clinical factor has been identified that can reliably explain or predict such variation. In recent years there has been growing interest in the possibility that genetic factors may play a role in the variability in opioid response. The aims of this review are to present the evidence supporting pharmacogenetic research in this area, to evaluate some of the studies and results that have been published to date and to present some of the challenges for future research in this area.

Spatial and temporal variations in silver contamination and toxicity in San Francisco Bay.

Although San Francisco Bay has a "Golden Gate", it may be argued that it is the "Silver Estuary". For at one time the Bay was reported to have the highest levels of silver in its sediments and biota, along with the only accurately measured values of silver in solution, of any estuarine system. Since then others have argued that silver contamination is higher elsewhere (e.g., New York Bight, Florida Bay, Galveston Bay) in a peculiar form of pollution machismo, while silver contamination has measurably declined in sediments, biota, and surface waters of the Bay over the past two to three decades. Documentation of those systemic temporal declines has been possible because of long-term, ongoing monitoring programs, using rigorous trace metal clean sampling and analytical techniques, of the United States Geological Survey and San Francisco Bay Regional Monitoring Program that are summarized in this report. However, recent toxicity studies with macro-invertebrates in the Bay have indicated that silver may still be adversely affecting the health of the estuarine system, and other studies have indicated that silver concentrations in the Bay may be increasing due to new industrial inputs and/or the diagenetic remobilization of silver from historically contaminated sediments being re-exposed to overlying surface waters and benthos. Consequently, the Bay may not be ready to relinquish its title as the "Silver Estuary".

Gabapentin is effective in the treatment of cancer-related neuropathic pain: a prospective, open-label study.

BACKGROUND: Gabapentin has been evaluated in the treatment of nonmalignant neuropathic pain, however, there is little direct evidence evaluating its efficacy in cancer-related neuropathic pain. OBJECTIVE: This study evaluated the effectiveness of gabapentin to treat cancer-related neuropathic pain. DESIGN: This was an open-label study. Two parallel groups of patients were recruited with either treatment-related (radiotherapy, surgery, chemotherapy) or tumor-related neuropathic pain. Gabapentin was dose-escalated from 300 mg/d to 1.8 g/d. MEASUREMENTS: The primary outcome, pain, was assessed using the modified brief pain inventory. In addition patient descriptors of pain and scores of activities of daily living were collated together with demographic data. RESULTS: We recruited 62 patients with treatment-related (n = 25) or tumor-related (n = 37) neuropathic pain. There was a significant reduction in the worst, average, and current pain scores (p < 0.002), but not the least pain score (p = 0.21). Twenty-eight of 62 (45.2%) of patients achieved at least a one third reduction in pain score (95% confidence interval [CI] 32.5-58.3); the number needed to treat to obtain this benefit is 2.2 (95% CI 1.7-3.1). There was a significant reduction in all scores measuring the impact of pain on daily living (p < 0.003). There was no significant difference in pain scores at day 8 compared to day 15. Analysis of variance suggested that gender, but not etiology, or type of neuropathic pain, was a significant predictor of analgesic response and this warrants further investigation. CONCLUSION: We conclude that gabapentin is an effective treatment for cancer-related neuropathic pain.

Clinical response to morphine in cancer patients and genetic variation in candidate genes.

Morphine is the analgesic of choice for moderate to severe cancer pain; however, 10-30% of patients do not tolerate morphine. This study evaluated genetic variation in the mu-opioid receptor, betaarrestin2, stat6 and uridine diphosphate-glucuronysltransferase 2B7 (UGT2B7) genes, in patients who responded to morphine vs those who were switched to alternative opioids. We prospectively recruited and genotyped 162 Caucasian patients (117 controls, 39 switchers). Switchers, were more likely to carry the common allele at 1182 G/A, 5864 G/A, 8622T/C and 11143 G/A in the betaarrestin2 gene (P = 0.021, 0.043, 0.013, 0.043, respectively). Switchers had increased carriage of the T allele (-1714 C/T) and a significant difference in the allelic frequency at 9065 C/T (chi(2) = 3.86, P = 0.049) in the stat6 gene. No differences were seen in genotype or allele frequencies of SNPs in the mu-opioid receptor gene or UGT2B7 gene. This study presents novel data suggesting that variation in genes involved in mu-opioid receptor signalling influence clinical response to morphine.

Systematic review of bisphosphonates for hypercalcaemia of malignancy.

BACKGROUND: Bisphosphonates are the treatment of choice for hypercalcaemia of malignancy (HCM) but there is no consensus regarding which drug or dose should be given. We designed a systematic review to investigate the efficacy of bisphosphonates in the treatment of HCM. METHODS: We identified randomized controlled trials (RCTs) by searching electronic databases, scanning of reference lists, and consultation with experts and pharmaceutical companies. Foreign papers were translated. Inclusion criteria were RCTs, confirmed malignant disease and measurement of serum calcium (ionized or corrected for albumin) postrehydration. The primary outcome was number of patients achieving normocalcaemia. Secondary outcomes were time to normocalcaemia, time to relapse and toxicity. RESULTS: Twenty-seven papers and two abstracts, using intravenous bisphosphonates, fulfilled the inclusion criteria. Data from 26 studies were used in analyses. Due to the heterogeneity of studies, meta-analysis could not be performed. Pamidronate was more effective than placebo, mithramycin, etidronate (7.5 mg/kg) and low-dose clodronate (600 mg), but equal to higher dose clodronate (1500 mg). Clodronate and etidronate were superior to placebo; incadronate was superior to elcatonin; gallium nitrate was superior to etidronate. No difference was seen between alendronate and clodronate. Three dose finding studies showed no difference between 30-90 mg of pamidronate, but one well designed study showed increasing efficacy with increasing dose. Studies using increasing doses of ibandronate (0.6-4 mg), alendronate (2.5-15 mg), and incadronate (2.5-10mg), showed a dose response. Duration of administration of pamidronate did not affect efficacy (six studies). CONCLUSION: Bisphosphonates normalize calcium in >70% patients with minimal side effects. Aminobisphosphonates are most effective at maintaining normocalcaemia and should be given in high dose irrespective of baseline serum calcium.

A retrospective study of the association between haematological and biochemical parameters and morphine intolerance in patients with cancer pain.

BACKGROUND: Morphine is the strong opioid of choice for the treatment of moderate to severe cancer pain according to guidelines of the World Health Organization (WHO). However, a minority of patients do not receive the desired analgesic effect or suffer intolerable side effects from morphine, and are switched to alternative opioids. METHODS: The aim of this retrospective study was to identify factors that might be associated with morphine intolerance. Data were analysed from 100 controls who tolerated morphine and 77 patients who were switched to an alternative opioid. We investigated whether currently logged data could fully explain the need to switch. Demographic details, cancer type (histological diagnosis) and markers related to organ function were included in an analysis of biochemical and haematological parameters. RESULTS: Patients over 78 years (P = 0.03), or with a high white cell (P = 0.002) or high platelet count (P = 0.003), were more likely to switch. Although our numbers were small, patients with severe organ impairment were more likely to switch. However, a model including white cell count, platelet count, age, serum albumin and alkaline phosphatase, accurately separated switchers and controls in only 68% of cases. There was no significant difference between the two groups in terms of the numbers of patients having cytotoxic drugs in the two weeks prior to the haematological and biochemical analysis. Similarly, there were no significant differences in histological diagnoses between groups. CONCLUSIONS: The white cell count was the strongest single effect observed and, as such, warrants further investigation. Further studies are needed in order to accurately define a model that will predict those patients likely to be intolerant of morphine.

A systematic review of the role of bisphosphonates in metastatic disease.

OBJECTIVES: To identify evidence for the role of bisphosphonates in malignancy for the treatment of hypercalcaemia, prevention of skeletal morbidity and use in the adjuvant setting. To perform an economic review of current literature and model the cost effectiveness of bisphosphonates in the treatment of hypercalcaemia and prevention of skeletal morbidity. DATA SOURCES: Electronic databases (1966-June 2001). Cochrane register. Pharmaceutical companies. Experts in the field. Handsearching of abstracts and leading oncology journals (1999-2001). REVIEW METHODS: Two independent reviewers assessed studies for inclusion, according to predetermined criteria, and extracted relevant data. Overall event rates were pooled in a meta-analysis, odds ratios (OR) were given with 95% confidence intervals (CI). Where data could not be combined, studies were reported individually and proportions compared using chi-squared analysis. Cost and cost-effectiveness were assessed by a decision analytic model comparing different bisphosphonate regimens for the treatment of hypercalcaemia; Markov models were employed to evaluate the use of bisphosphonates to prevent skeletal-related events (SRE) in patients with breast cancer and multiple myeloma. RESULTS: For acute hypercalcaemia of malignancy, bisphosphonates normalised serum calcium in >70% of patients within 2-6 days. Pamidronate was more effective than control, etidronate, mithramycin and low-dose clodronate, but equal to high dose clodronate, in achieving normocalcaemia. Pamidronate prolongs (doubles) the median time to relapse compared with clodronate or etidronate. For prevention of skeletal morbidity, bisphosphonates compared with placebo, significantly reduced the OR for fractures (OR [95% CI], vertebral, 0.69 [0.57-0.84], non-vertebral, 0.65 [0.54-0.79], combined, 0.65 [0.55-0.78]) radiotherapy 0.67 [0.57-0.79] and hypercalcaemia 0.54 [0.36-0.81] but not orthopaedic surgery 0.70 [0.46-1.05] or spinal cord compression 0.71 [0.47-1.08]. However, reduction in orthopaedic surgery was significant in studies that lasted over a year 0.59 [0.39-0.88]. Bisphosphonates significantly increased the time to first SRE but did not affect survival. Subanalyses were performed for disease groups, drugs and route of administration. Most evidence supports the use of intravenous aminobisphosphonates. For adjuvant use of bisphosphonates, Clodronate, given to patients with primary operable breast cancer and no metastatic disease, significantly reduced the number of patients developing bone metastases. This benefit was not maintained once regular administration had been discontinued. Two trials reported significant survival advantages in the treated groups. Bisphosphonates reduce the number of bone metastases in patients with both early and advanced breast cancer. Bisphosphonates are well tolerated with a low incidence of side-effects. Economic modelling showed that for acute hypercalcaemia, drugs with the longest cumulative duration of normocalcaemia were most cost-effective. Zoledronate 4 mg was the most costly, but most cost-effective treatment. For skeletal morbidity, Markov models estimated that the overall cost of bisphosphonate therapy to prevent an SRE was GBP250 and GBP1500 per event for patients with breast cancer and multiple myeloma, respectively. Bisphosphonate treatment is sometimes cost-saving in breast cancer patients where fractures are prevented. CONCLUSIONS: High dose aminobisphosphonates are most effective for the treatment of acute hypercalcaemia and delay time to relapse. Bisphosphonates significantly reduce SREs and delay the time to first SRE in patients with bony metastatic disease but do not affect survival. Benefit is demonstrated after administration for at least 6-12 months. The greatest body of evidence supports the use of intravenous aminobisphosphonates. Further evidence is required to support use in the adjuvant setting.

Systematic review of role of bisphosphonates on skeletal morbidity in metastatic cancer.

OBJECTIVE: To review the evidence for the use of bisphosphonates to reduce skeletal morbidity in cancer patients with bone metastases. DATA SOURCES: Electronic databases, scanning reference lists, and consultation with experts and pharmaceutical companies. Foreign language papers were included. STUDY SELECTION: Included trials were randomised controlled trials of patients with malignant disease and bone metastases who were treated with oral or intravenous bisphosphonate compared with another bisphosphonate, placebo, or standard care. All trials measured at least one outcome of skeletal morbidity. RESULTS: 95 articles were identified; 30 studies fulfilled inclusion criteria. In studies that lasted > or = 6 months, compared with placebo bisphosphonates significantly reduced the odds ratio for fractures (vertebral 0.69, 95% confidence interval 0.57 to 0.84, P < 0.0001; non-vertebral 0.65, 0.54 to 0.79, P < 0.0001; combined 0.65, 0.55 to 0.78, P < 0.0001), radiotherapy (0.67, 0.57 to 0.79, P < 0.0001), and hypercalcaemia (0.54, 0.36 to 0.81, P = 0.003) but not for orthopaedic surgery (0.70, 0.46 to 1.05, P = 0.086) or spinal cord compression (0.71, 0.47 to 1.08, P = 0.113). The reduction in orthopaedic surgery was significant in studies that lasted over a year (0.59, 0.39 to 0.88, P = 0.009). Use of bisphosphonates significantly increased time to first skeletal related event but did not increase survival. Subanalyses showed that most evidence supports use of intravenous aminobisphosphonates. CONCLUSIONS: In people with metastatic bone disease bisphosphonates significantly decrease skeletal morbidity, except for spinal cord compression and increased time to first skeletal related event. Treatment should start when bone metastases are diagnosed and continue until it is no longer clinically relevant.