The safety and efficacy of benzbromarone in gout in Aotearoa New Zealand.

BACKGROUND: Benzbromarone is a potent uricosuric but is not widely available due to concerns about hepatotoxicity. In Aotearoa New Zealand, benzbromarone has been available since April 2013, subject to funding restrictions, for patients with inadequate urate-lowering response or intolerance to allopurinol and probenecid. AIM: To assess the safety and efficacy of benzbromarone in a real-life setting. METHODS: All patients who received funding for benzbromarone from 1 April 2013 to 30 September 2014 were identified. Prescribers were sent a questionnaire for each individual. Information on demographics, efficacy of previous urate-lowering drugs and reasons for discontinuation were collected. Specific information about the dose, effect on serum urate, adverse effects and liver function tests after commencing benzbromarone was recorded. RESULTS: Completed questionnaires were returned for 123 of 164 (75%) patients. Mean (SD) serum urate prior to benzbromarone was 0.57 (0.12) mmol/L, and estimated glomerular filtration rate was 50.3 (22.8) mL/min/1.73 m(2) . The median dose of benzbromarone was 100 mg/day (25-200 mg/day). Six months after commencing benzbromarone, mean (SD) serum urate was 0.35 (0.12) mmol/L. Benzbromarone-related adverse events included rash (n = 4), diarrhoea (n = 9), nausea (n = 6) and urate stones (n = 3). Liver function test abnormalities were uncommon and tended to be mild. There were 14 patient deaths; none was considered related to benzbromarone. Allopurinol had been prescribed prior to benzbromarone in 117 of 123 patients; median maximum allopurinol dose was 200 mg/day (range 25-600 mg/day), and 19% patients received allopurinol >300 mg/day. CONCLUSION: Benzbromarone provides useful urate-lowering efficacy and does not appear unsafe in patients with gout. Urate-lowering therapy prescribing requires further optimisation.

Transurethral resection of the prostate--"now and then".

The number of transurethral resections of the prostate (TURP) performed each year is decreasing. The aim of this study was to assess a cohort of patients undergoing TURP and compare this to one twenty years earlier in terms of procedure, complications and outcomes. A retrospective comparative analysis of one hundred consecutive TURPs performed in 2010 was compared to one hundred cases performed in 1990. Fifty-five (55%) had a urinary catheter (UC) in situ pre-operatively in 2010 compared to 22 (22%) in 1990. The length of catheterisation time was significantly longer in 2010 compared with 1990 (average 65 days vs 20 days). Infective complications occurred in six (6%) patients in 2010 and three (3%) in the 1990 cohort. Patients who had UCs in situ preoperatively for longer periods had a higher rate of infective complications and more serious complications. This highlights the importance of early specialist referral for patients diaqnosed with urinary retention.

A patient reported outcome measure (PROM) assessing quality of care in the urology hospital outpatient setting.

A prospective blind PROM (patient reported outcome measure) study performed in our urology department examined the outpatient-clinic experience. 104 questionnaires were completed. 23 patients (22%) felt the waiting times for appointments was excessive. 13 patients (13%) experienced difficulty in contacting administrative staff. 98 patients (94%) considered the waiting areas good but 31 patients (31%) considered lack of privacy an issue. Consultants saw 65 patients (63%). 62 patients (60%) expected to be seen by a consultant. 32 patients (31%) felt consultation with a different doctor on return visits was unsatisfactory. 76 patients (73%) "fully trusted" their doctors. 78 patients (75%) rated their visit excellent, 10 patients (10%) added comments. Despite frustration with waiting times, the experience of patients reflects a positive rapport and trust between patient and doctor.

'I think we just do it once and leave it ' The collection and utility of family health history in general practice in Aotearoa New Zealand: a qualitative study.

Introduction The value of family health history as a means to understanding health risk has been long known. Its value in a precision medicine context is also now becoming apparent. General practitioners (GPs) are considered to play a key role in the collection, and investigation, of family health history, but it remains widely reported as being both poorly and infrequently undertaken. Little is known about this practice in Aotearoa New Zealand (NZ). Aim This study aimed to explore current practices in relation to the ascertainment of family health history, with a view towards precision medicine. Methods Semi-structured interviews were conducted with 10 GPs recruited from one urban area of NZ. The interviews were subjected to a thematic analysis. Results Family health history information was used to varying degrees in four areas - risk ascertainment, patient engagement with a diagnosis, social context and building relationships. Patient cultural considerations were rarely mentioned. Reliability of information provided by patients, resource constraints, context driven consults and electronic health record limitations are potential indicators of current limits of family health history. Discussion Our findings present a baseline of current practice and echo larger studies from overseas. As precision medicine is not yet routine, a unique opportunity exists for consideration to be given to establishing specific roles within the NZ health system to enable equitable practice of, and subsequent health gains from, the use of family/whanau health history information as part of precision medicine.

Ureteric angioplasty balloon placement to increase localised dosage of BCG for renal pelvis TCC.

Endoscopic percutaneous resection of a renal pelvis transitional cell carcinoma (TCC) is a viable treatment option in those who would be rendered dialysis dependent following a nephroureterectomy. We report endoscopic percutaneous resection of an upper tract TCC recurrence in a single functioning kidney followed by antegrade renal pelvis BCG instillation with novel placement of inflated angioplasty balloon in the ureter to help localise its effect.

Scrotal signs and symptoms in the general population, the value of testis self-examination and the pitfalls of a scrotal screening programme: is the two-week rule relevant?

PURPOSE: Testicular symptoms/lumps are a cause of concern, anxiety and possible diagnostic dilemma for patient and general practitioner. The majority of scrotal pathology is benign in nature and results in a huge workload. The main aim of this study was to determine the relationship between scrotal symptoms, previous scrotal surgery, testicular self-examination and awareness of scrotal abnormalities. Secondarily, we sought to determine the scrotal findings in men enrolled in a consultant urologist-directed screening programme. METHODS: There were 677 men surveyed on their performance of TSE. They were also asked about scrotal symptoms and prior surgery, before undergoing blinded physical examination by one of four consultant urologists. RESULTS: Among the participants, 9.8% of men had scrotal symptoms with 55% of these having a normal scrotal examination and the rest having benign pathology. A number of men who had undergone previous scrotal surgery (13%) had no clinical findings detected on scrotal examination. No subject was found to have testis cancer; 20.9% had a benign scrotal or inguinal condition detected with the majority (65%) not aware of the abnormality. Men who demonstrate a superior awareness of their scrotal abnormalities were more likely to perform TSE. CONCLUSIONS: Increased awareness of scrotal abnormalities combined with TSE may have a role in improving detection of significant testicular pathology. However, the high prevalence of benign scrotal conditions, of which most men were unaware, may serve to raise anxiety in the patient and general practitioner. We believe there is no role for a one-stop scrotal anxiety clinic, as the costs do not justify the benefits.

Extended long term functional outcome of inflatable penile prosthesis in a single institution.

We sought to evaluate the extended long term functional outcome of the AMS700 three piece inflatable prosthesis in men with erectile dysfunction in a single urological department and assess our revision rates. Patients that underwent first-time insertion or revision of an AMS700 3 piece inflatable penile prosthesis between 1984-2007 were included. Data was obtained from medical records and long term follow up of patients was conducted by telephone interview. The medical records of 38 patients were available for review. Of these 38 men, 56 prostheses were inserted. The mean follow up was 8.4 years (101 months). The revision rate at 50 months postoperatively was 7/38 (18%). The overall revision rate was 18/38 (47%). The mean time to revision in these 18 patients was 72 months (12-156 months) after initial insertion of AMS700 penile prosthesis. This study highlights that with longer follow u revision rates markedly increase after 72 months.

'I think there is nothing . . . that is really comprehensive': healthcare professionals' views on recommending online resources for pain self-management.

OBJECTIVES: To explore healthcare professionals' views on, and attitudes, towards recommending online resources for persistent pain self-management. METHODS: This study was the qualitative phase of a two-phase mixed method study. Thirty-one New Zealand health professionals involved in the management of persistent pain were interviewed via focus groups and individual interviews. Data were analysed using the general inductive approach. RESULTS: The major themes were as follows: (1) risks and limits of online information outweigh benefits, (2) a blended model, of online resources with healthcare professional support, could work, (3) only trustworthy resources can be recommended, (4) need for personalisation and (5) perceived barriers to adoption. CONCLUSION: Online resources were perceived as a useful adjunct to support pain self-management; however, due to potential risks of misinterpretation and misinformation, healthcare professionals proposed a 'blended model' where curated online resources introduced during face-to-face consultations could be used to support self-management. Participants needed 'trustworthy online resources' that provide evidence-based, updated information that is personalised to clients' health literacy and cultural beliefs. PRACTICE IMPLICATIONS: Training for healthcare professionals on critical appraisal of online resources or curation of evidence-based online resources could increase recommendation of online resources to support pain self-management as an adjunct to in-person care.

Mechanisms of glucose intolerance in cystic fibrosis.

AIMS: Although cystic fibrosis-related diabetes (CFRD), a poor prognostic factor in cystic fibrosis (CF), is characterized by insulinopenia, the role of insulin resistance is unclear. Using a prospective study design, we measured insulin resistance, pancreatic beta-cell function and correlated glycaemic status with clinical parameters. METHODS: Oral glucose tolerance test was performed in 60 stable adult CF patients. Insulin sensitivity and beta-cell function were measured using the homeostatic model assessment (HOMA2), Stumvoll and oral glucose insulin sensitivity (OGIS) indices. RESULTS: Forty-two (70%) had normal glucose tolerance (NGT), 10 (17%) impaired glucose tolerance (IGT) and eight (13%) CFRD. There was no difference in insulin sensitivity among the three groups (HOMA2: NGT 280, IGT 250, CFRD 339, P = 0.42; Stumvoll: NGT 0.128, IGT 0.126, CFRD 0.129, P = 0.76; and OGIS: NGT 515, IGT 472, CFRD 472, P = 0.12). Pancreatic beta-cell function (CFRD 50% vs. NGT 67%; P < 0.05) and first-phase insulin secretion were reduced in CFRD (250 vs. NGT 509; P = 0.004). First-phase insulin secretion was inversely correlated with 1-h (r = -0.74; P < 0.0001) and 2-h glucose levels (r = -0.34; P < 0.05). There was no difference in body mass index or poor lung function (forced expiratory volume in 1 s: CFRD 54% vs. NGT 65%; P = 0.43). However, there were more hospital admissions in the CFRD group (three vs. NGT one per patient per year; P < 0.05). CONCLUSIONS: CFRD is characterized by qualitative and quantitative defects in insulin secretion, but not insulin resistance, and is associated with increased hospital admissions for pulmonary exacerbations.

Differential stability of Drosophila embryonic mRNAs during subsequent larval development.

The relative stabilities of specific embryonic mRNAs that persist in Drosophila melanogaster larvae were determined using an approach that combined RNA density labeling with cell-free translation. Unlike the other methods commonly used to measure the decay of individual mRNAs, the density labeling approach does not depend on the use of transcriptional inhibitors or on the measurement of precursor pool specific activities. Using this approach, we have determined that different embryonic mRNA species persist for varying periods during subsequent development, with half-lives ranging from approximately 2 to approximately 30 h. The embryonic histone mRNAs are relatively unstable; they are no longer detectable by 9 h of larval development. By 41 h of larval development, 90% of the nonhistone mRNAs assayed have decayed considerably; computerized scanning densitometry of translation products indicates that these transcripts are not decaying as members of discrete half-life classes. The persisting mRNAs that remain are very long-lived; their in vitro translation products can still be detected after 91 h of larval development. We have tentatively identified the mRNAs that encode actin, tropomyosin, and tubulin as members of this stable mRNA population. Although embryonic mRNAs do fall into these three broad classes of stability, they appear to decay with a continuum of half-lives. Because the range of half-lives is so great, mRNA stability is probably an important factor controlling mRNA abundance during Drosophila development.

An unusual penpal: case report and literature review of posterior urethral injuries secondary to foreign body insertion.

We report the case of a 57-year-old male who attended the emergency department after inserting a ballpoint pen into his urethra 24 hours earlier during a sexual encounter. Rigid cystoscopy was performed and confirmed the foreign body to have caused a partial rupture of the posterior urethra. It was subsequently removed using a combination of graspers and stone retrieval baskets. Self insertion of foreign bodies into the urethra is often as a result of psychiatric disturbance, alcohol intoxication or as a means of sexual gratification. Posterior urethral injuries are more commonly associated with pelvic trauma and iatrogenic injuries. Injury secondary to self insertion of a foreign body is infrequently reported. Temporary insertion of a urethral catheter may be necessary. We reviewed the literature in relation to this unusual problem.

Approaches to the detection of Clostridioides difficile in the healthcare environment.

Clostridioides difficile, a spore-forming bacillus, is a major cause of healthcare-associated infection, and can survive for prolonged periods in the inanimate environment. Environmental sampling to detect C. difficile is not routine but may be undertaken as part of outbreak management and during research projects. We conducted a literature search covering the period between 1980 and 2018 to review methods for the detection of this pathogen in the environment. There are many acceptable sampling methods used for environmental screening, including contact plates, cotton swabs, flocked swabs and sponges. Most recent studies suggest that sponges are the most effective method of sampling and have the added benefit of being capable of sampling larger and curved areas. Culture methods are the most common laboratory method of detecting C. difficile from environmental samples. However, the results are variable depending on the type of agar used and the turnaround times can be long. Molecular methods such as real-time polymerase chain reaction (RT-PCR), although more commonly used to detect C. difficile from faecal specimens, has been used with varying degrees of success in environmental sampling. Further studies are needed to determine whether molecular techniques could offer a more reliable, faster method of environmental sampling, giving infection prevention and control teams more reassurance that patients are being placed in adequately decontaminated hospital environments.

A labile period in the determination of the anterior-posterior axis during early neural development in Xenopus.

The process by which the vertebrate central nervous system acquires its regional properties remains a central problem in developmental biology. It is generally argued that at early gastrula stages the dorsal mesoderm possesses precise anterior-posterior positional information, which is subsequently imparted to the overlying ectoderm. However, using regionally specific gene probes to monitor regional responses in Xenopus embryos, we find that anterior-posterior properties are not fixed until early neurula stages. During gastrulation the regional inducing capacities of the dorsal mesoderm as well as the regional responses of the presumptive neural ectoderm are activated along the entire anterior-posterior axis when these properties are assayed in recombinant and explant experiments, respectively. Restriction of regional inducing capacity in the mesoderm and responsiveness in the neural ectoderm occur only at neural plate stages.

A modified Delphi exercise to determine the extent of consensus with OMERACT outcome domains for studies of acute and chronic gout.

OBJECTIVES: To reach consensus with recommendations made by an OMERACT Special Interest Group (SIG). METHODS: Rheumatologists and industry representatives interested in gout rated and clarified, in three iterations, the importance of domains proposed by the OMERACT SIG for use in acute and chronic gout intervention studies. Consensus was defined as a value of less than 1 of the UCLA/RAND disagreement index. RESULTS: There were 33 respondents (61% response rate); all agreed the initial items were necessary, except "total body urate pool". Additional domains were suggested and clarification sought for defining "joint inflammation" and "musculoskeletal function". Items that demonstrated no clear decision were re-rated in the final iteration. There were six highly rated items (rating 1-2) with four slightly lower rating items (rating 3) for acute gout; and 11 highly rated items with eight slightly lower ratings for chronic gout. CONCLUSIONS: Consensus is that the following domains be considered mandatory for acute gout studies: pain, joint swelling, joint tenderness, patient global, physician global, functional disability; and for chronic gout studies: serum urate, gout flares, tophus regression, health-related quality of life, functional disability, pain, patient global, physician global, work disability and joint inflammation. Several additional domains were considered discretionary.

Colchicine suppresses neutrophil superoxide production in a murine model of gouty arthritis: a rationale for use of low-dose colchicine.

BACKGROUND AND PURPOSE: When used to treat gouty arthritis, colchicine is believed to work by inhibiting microtubule-dependent cell infiltration. However, in vitro, colchicine also reduces monosodium urate (MSU)-induced superoxide production by neutrophils. Our study aimed to compare the effects of colchicine on neutrophil superoxide production and infiltration in an in vivo model of acute gouty inflammation. EXPERIMENTAL APPROACH: In vitro: Human and murine peritoneal neutrophils were incubated with MSU with and without colchicine, and superoxide production was measured. In vivo: Mice were treated with colchicine followed by an intraperitoneal injection of MSU to induce acute inflammation. After 4h, the peritoneal cells were recovered to measure superoxide production and neutrophil infiltration. Sera were tested for liver and renal toxicity. KEY RESULTS: Colchicine dose-dependently inhibited MSU-induced superoxide production by both human and murine neutrophils in vitro. Oral colchicine inhibited MSU-induced superoxide production by neutrophils in vivo at doses 100 times lower than those required to inhibit neutrophil infiltration and without acute liver or renal toxicity. Neutrophils treated with colchicine in vivo still produced superoxide in response to another stimulus, 4-beta-phorbol-12-myristate-13-acetate. CONCLUSIONS AND IMPLICATIONS: These results show a beneficial effect of colchicine for the treatment of MSU-induced superoxide production in vivo at sub-toxic doses without compromising superoxide production by other physiological processes. This is the first in vivo data to provide a biological rationale that supports the implementation of low dose, non-toxic, colchicine therapy for the treatment of gouty arthritis.

Vertebrate eye development.

Vertebrate eye determination is mediated by a series of inductive interactions that have now been more precisely defined with the use of regional markers. Analyses of the genes responsible for eye mutations and the cloning of genes delimiting spatial domains within the developing eye have begun to elucidate the molecular basis of this process.

Embryonic lens induction: shedding light on vertebrate tissue determination.

The principle of embryonic induction was defined by early studies of lens determination, and because of the relative simplicity of the developing lens and its interaction with presumptive retinal tissue it has been a favored system for examining mechanisms of induction. Recent studies have led to substantial alterations of the classic model for this process, introducing several elements that significantly refine our view of vertebrate tissue determination.

Assessment of outcome in clinical trials of gout--a review of current measures.

There has been renewed interest in the treatment of gout with recent reported intervention studies of new agents such as etoricoxib, febuxostat and pegylated-uricase. However, these studies have highlighted the relative paucity of validated outcome measures with which to judge efficacy. This review outlines the published information regarding which endpoints have been measured in randomized clinical trials, what should be measured, what tools or instruments are available for this and the technical properties of such instruments. It highlights recent work that validates measures of tophi, radiographic damage and patient-reported outcomes. The absence of a valid definition of gout-flare or how flare reduction defines response is problematic; this forms the basis for a current ACR-EULAR sponsored project.

Xenopus gamma-crystallin gene expression: evidence that the gamma-crystallin gene family is transcribed in lens and nonlens tissues.

Crystallins, the major gene products of the lens, accumulate to high levels during the differentiation of the vertebrate lens. Although crystallins were traditionally thought to be lens specific, it has recently been shown that some are also expressed at very low levels in nonlens tissues. We have examined the embryonic expression pattern of gamma-crystallins, the most abundant crystallins of the embryonic lens in Xenopus laevis. The expression profile of five Xenopus gamma-crystallin genes mirrors the pattern of lens differentiation in X. laevis, exhibiting on average a 100-fold increase between tailbud and tadpole stages. Four of these genes are also ubiquitously expressed outside the lens at a very low level, the first demonstration of nonlens expression of any gamma-crystallin gene; expression of the remaining gene was not detected outside the head region, thus suggesting that there may be two classes of gamma-crystallin genes in X. laevis. Predictions regarding control mechanisms responsible for this dual mode of expression are discussed. This study raises the question of whether any crystallin, on stringent examination, will be found exclusively in the lens.

Developmental regulation of hypomethylation of delta-crystallin genes in chicken embryo lens cells.

Sequences in the two delta-crystallin genes become hypomethylated when they are expressed in the chick lens. This system is particularly advantageous for studying temporal changes in hypomethylation, since lens tissue can be isolated at all developmental stages. In previous work we have shown that most HpaII sites become hypomethylated within the delta 1-crystallin gene long after delta-crystallin gene activation. One site is hypomethylated when crystallin mRNA begins to be synthesized at high levels at 50 h; we show here that this site maps to the 3' end (intron 15) of the delta 1-crystallin gene. In addition, we have examined the methylation status of HpaII and HhaI sites found near the 5' end of the delta 1-crystallin gene. Two HhaI sites adjacent to a viral core enhancer sequence in intron 2 are also first hypomethylated at 50 h. These findings point to regions of the delta 1 gene that should be investigated further for functional significance in regulating delta-crystallin transcription.