Obtaining a genetic diagnosis via genetic testing (GT) is a fundamental step in determining the eligibility of a patient to be enrolled in emerging clinical trials and research studies. Besides, the ...knowledge of genetic outcome allows patients to plan for significant life choices. However, critical barriers exist to an equitable access to genetic services globally. The objective of this study was to explore patient experiences while seeking genomic services for inherited retinal degenerations (IRDs).
An online survey was designed based on a focus group conducted by Retina International and including people affected by IRDs and their families living in different regions around the world. The survey was then circulated to 43 Retina International member organisations globally via email newsletters and social networks. The survey involved questions in relation to the accessibility, affordability, and timeliness of genomic services for IRDs as well as patient perceived awareness of genomic services for IRDs among healthcare professionals.
A total of 410 respondents (IRD patients and caregivers) from over 30 countries across all continents responded to the survey. A considerable number of the patients had to go through a long and arduous journey to access GT and counselling services, wherein 40% had to visit more than 5 physicians, 27% had to visit more than 5 clinics, and 57% had to wait for more than 3 years before obtaining a genetic diagnosis. Furthermore, 46% of respondents reported not receiving genetic counselling prior to undergoing GT, and 39% reported not receiving genetic counselling after undergoing GT. Over 3/4th of the participants reported that they did not have to pay for their genomic services for IRDs. Thirty-seven percent of the respondents reported that their eye care professionals (ECPs) were either not aware of GT, remained neutral, or did not encourage them to undergo GT.
Patients with IRDs do not have equitable access to best practice GT and counselling services. Greater awareness and training regarding IRDs and the benefits of GT and genetic counselling for patients and families are needed among ECPs. A best practice model on access to genomic services for IRDs is required.
Almost all of the 820,000 people in the UK with dementia will experience Behavioural and Psychological Symptoms of Dementia (BPSD). However, research has traditionally focused on treating cognitive ...symptoms, thus neglecting core clinical symptoms that often have a more profound impact on living with dementia. Recent evidence (Kales et al, 2007; Ballard et al, 2009) indicates that the popular approach to managing BPSD - prescription of anti-psychotic medication - can increase mortality and the risk of stroke in people with dementia as well as impair quality of life and accelerate cognitive decline. Consequently, there is a need to evaluate the impact that non-pharmacological interventions have on BPSD; we believe physical exercise is a particularly promising approach.
We will carry out a pragmatic, randomised, single-blind controlled trial to evaluate the effectiveness of exercise (planned walking) on the behavioural and psychological symptoms of individuals with dementia. We aim to recruit 146 people with dementia and their carers to be randomized into two groups; one will be trained in a structured, tailored walking programme, while the other will continue with treatment as usual. The primary outcome (BPSD) will be assessed with the Neuropsychiatric Inventory (NPI) along with relevant secondary outcomes at baseline, 6 and 12 weeks.
Designing this study has been challenging both ethically and methodologically. In particular to design an intervention that is simple, measurable, safe, non-invasive and enjoyable has been testing and has required a lot of thought. Throughout the design, we have attempted to balance methodological rigour with study feasibility. We will discuss the challenges that were faced and overcome in this paper.
ISRCTN01423159.
Dactinomycin (actinomycin D) is an antitumor antibiotic used routinely to treat certain pediatric and adult cancers. Despite concerns over the incidence of toxicity, little is known about the ...pharmacology of dactinomycin. A study was done to investigate dactinomycin pharmacokinetics in children.
Dactinomycin was administered to 31 patients by bolus i.v. infusion, at doses of 0.70 to 1.50 mg/m2. Plasma concentrations were determined by liquid chromatography-mass spectrometry up to 24 hours after drug administration and National Cancer Institute Common Toxicity Criteria was assessed.
Pharmacokinetic data analysis suggested that a three-compartment model most accurately reflected dactinomycin pharmacokinetics. However, there was insufficient data available to fully characterize this model. A median peak plasma concentration (Cmax) of 25.1 ng/mL (range, 3.2-99.2 ng/mL) was observed at 15 minutes after administration. The median exposure (AUC0-6), determined in 16 patients with sampling to 6 hours, was 2.67 mg/L.min (range, 1.12-4.90 mg/L.min). After adjusting for body size, AUC0-6 and Cmax were positively related to dose (P = 0.03 and P = 0.04, respectively). Patients who experienced any level of Common Toxicity Criteria grade had a 1.46-fold higher AUC0-6, 95% confidence interval (1.02-2.09). AUC0-6 was higher in patients <40 kg, possibly indicating a greater toxicity risk.
Data presented suggest that dosing of dactinomycin based on surface area is not optimal, either in younger patients in whom the risk of toxicity is greater, or in older patients where doses are capped.
To assess the role of pars plana vitrectomy (PPV) for symptomatic vitreous opacification in a series of patients with Fuchs' heterochromic uveitis (FHU).
A retrospective review was undertaken of 13 ...patients with FHU who underwent vitrectomy for vitreous opacification between April 1989 and December 1998.
An improvement in visual symptoms was recorded in all patients, 9 of 13 (69%) demonstrating at least a 2 line increase in Snellen visual acuity. All but one patient attained 6/9 or better visual acuity post-operatively. Surgery was uneventful and did not appear to exacerbate any existing intraocular inflammation.
From this series we conclude that PPV has an important role in the management of patients with FHU who present with symptomatic vitreous opacification.
Both of the title compounds, catena‐polytetraaquamagnesium(I)‐μ‐4,4′‐bipyridine‐κ2N:N′ diiodide bis(4,4′‐bipyridine) solvate, {Mg(C10H8N2)(H2O)4I2·2C10H8N2}n, (I), and ...catena‐polyμ‐4,4′‐bipyridine‐bisdiiodobis(propan‐1‐ol)strontium(I)‐di‐μ‐4,4′‐bipyridine‐κ4N:N′ bis(4,4′‐bipyridine) solvate, {Sr2I4(C10H8N2)3(C3H8O)4·2C10H8N2}n, (II), are one‐dimensional polymers which are single‐ and double‐stranded, respectively, the metal atoms being linked by the 4,4′‐bipyridine moieties. The Mg complex, (I), is cis‐{(H2O)4Mg(N‐4,4′‐bipyridine‐N′)(2/2)}(∞|∞)I2·4,4′‐bipyridine and Mg has a six‐coordinate quasi‐octahedral coordination environment. The Sr complex, (II), is isomorphous with its previously defined Ba counterpart Kepert, Waters & White (1996). Aust. J. Chem.49, 117–135, being (propan‐1‐ol)2I2Sr(N‐4,4′‐bipyridine‐N′)(3/2)(∞|∞)·4,4′‐bipyridine, with the I atoms trans‐axial in a seven‐coordinate pentagonal–bipyramidal Sr environment.
An approach to carboplatin dosing in children with bilateral nephrectomy using a renal function-based dosing formula with a glomerular filtration rate of zero was investigated in the current study. ...Carboplatin exposure was determined in a total of nine courses of chemotherapy in four patients with Wilms' tumour. Carboplatin exposures following initial dosing were less than 50% of the defined target area under the plasma concentration-time curve (AUC) in all four patients studied, with actual AUC values of between 31% and 45% of the target exposures. The use of real-time pharmacokinetic monitoring to guide dosing within a course of carboplatin treatment resulted in exposures within 15% of the target AUC in all patients. Using this information to guide dosing on additional courses of treatment in the same patient resulted in consistent exposures without the need for further monitoring or dose adjustment. These results indicate that real-time pharmacokinetic monitoring of carboplatin treatment plays a key role in ensuring that an appropriate exposure to carboplatin is achieved in children with bilateral nephrectomy. Carboplatin dosing based on patient body weight, or use of a fixed dose of carboplatin, would both be predicted to result in individual patients receiving unsatisfactory drug exposures. Further studies are warranted to further elucidate the relationship between non-renal clearance of carboplatin and patient body weight in this and other patient subpopulations where there remains concern about the optimal way to use this anticancer drug.
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