Complete continence after botulinum neurotoxin type A injections for refractory idiopathic detrusor overactivity incontinence: patient-reported outcome at 4 weeks

Objective improvement following intradetrusor injections of botulinum neurotoxin type A (BoNTA) is well documented. Although patient-related outcome measures are highly recommended for monitoring overactive bladder symptoms, no study before has dealt with the question of patient-reported complete continence after BoNTA treatment using validated questionnaires.

(99m)Tc-DPD-SPECT/CT predicts the outcome of imaging-guided diagnostic anaesthetic injections: A prospective cohort study

We hypothesized that bone SPECT combined with multiplanar reconstructed CT can identify and target the pain-inducing focus in the foot and can be used to successfully guide anaesthetic infiltrations. Therefore we prospectively investigated feasibility and predictive value of bone SPECT/CT for image guided diagnostic infiltrations in patients with chronic foot pain.

Intradermal injection of heat-killed Mycobacterium vaccae in dogs with atopic dermatitis: a multicentre pilot study

Canine atopic dermatitis (cAD) is a common disease with a multifactorial aetiology associated with impaired immunoregulation. The immunopathogenesis has similarities to that of human atopic dermatitis. Clinical signs of allergic disease in humans and mice are reduced by administration of saprophytic mycobacteria that amplify regulatory cytokines and hence the effect of Mycobacterium vaccae on the clinical severity of cAD was investigated. Sixty-two dogs with cAD, selected according to strict criteria, were treated with a single intradermal injection and evaluated monthly for 3 months in a placebo-controlled double-blind clinical trial. Clinical severity was quantified using standardized scores and by owner assessment of pruritus. A single injection of a heat-killed suspension of M. vaccae was found to be well tolerated and effective in treating mild to moderate cases of cAD demonstrable for 3 months, but was insignificant in more severely affected dogs.

Clean intermittent self-catheterization after botulinum neurotoxin type A injections: short-term effect on quality of life

OBJECTIVE: To investigate the hypothesis that the need for clean intermittent self-catheterization after botulinum neurotoxin type A injections is outweighed by the efficacy of this treatment, so that clean intermittent self-catheterization is not a burden for patients with refractory idiopathic detrusor overactivity. METHODS: Women undergoing intradetrusor injections of 200 units botulinum neurotoxin type A for refractory idiopathic detrusor overactivity were evaluated prospectively. Clean intermittent self-catheterization was discussed with all patients and its possible need after botulinum neurotoxin type A treatment. As indicator of quality of life, lower urinary tract symptom distress and effect on daily activities were assessed using the validated Urogenital Distress Inventory (UDI-6) and Incontinence Impact Questionnaire (IIQ-7) before and 4 weeks after receiving botulinum neurotoxin type A injections. RESULTS: Mean age of the 65 women was 51 years, and all voided spontaneously before botulinum neurotoxin type A injections. After botulinum neurotoxin type A treatment, 28 (43%) required clean intermittent self-catheterization. Mean UDI-6 and IIQ-7 scores reduced from 61 to 33 (P<.001) and 62 to 30 (P<.001) in women performing clean intermittent self-catheterization and from 60 to 28 (P<.001) and 64 to 25 (P<.001) in those who did not, respectively. Comparison of quality of life in women performing clean intermittent self-catheterization and in those who did not revealed no significant differences before and after botulinum neurotoxin type A treatment. CONCLUSION: Clean intermittent self-catheterization after botulinum neurotoxin type A intradetrusor injections did not impair quality of life in appropriately informed and selected women in the short term. All patients should be informed of the potential need for clean intermittent self-catheterization after botulinum neurotoxin type A injections, and a willingness to do so should be a prerequisite for this still unlicensed off-label treatment.

In vitro allergy tests compared to intradermal testing in horses with recurrent airway obstruction

Recurrent airway obstruction (RAO) is a common condition in stabled horses characterised by small airway inflammation, airway neutrophilia and obstruction following exposure of susceptible horses to mouldy hay and straw and is thus regarded as a hypersensitivity reaction to mould spores. However, the role of IgE-mediated reactions in RAO remains unclear. The aim of the study was to investigate with a serological IgE ELISA test (Allercept), an in vitro sulfidoleukotriene (sLT) release assay (CAST) and with intradermal testing (IDT) whether serum IgE and IgE-mediated reactions against various mould, mite and pollen extracts are associated with RAO. IDT reactions were evaluated at different times in order to detect IgE-mediated immediate type reactions (type I hypersensitivity reactions, 0.5-1 h), immune complex-mediated late type reactions (type III reactions, 4-10 h) and cell-mediated delayed type reactions (type IV hypersensitivity reactions 24-48 h). In the serological test, overall the control horses displayed more positive reactions than the RAO-affected horses but the difference was not significant. Comparison of the measured IgE levels showed that the RAO-affected horses had slightly higher IgE levels against Aspergillus fumigatus than controls (35 and 16 AU, respectively, p<0.05), but all values were below the cut off (150 AU) of the test. In the sLT release assay, seven positive reactions were observed in the RAO-affected horses and four in the controls but this difference was not significant. A significantly higher proportion of late type IDT reactions was observed in RAO-affected horses compared to controls (25 of 238 possible reactions versus 12 of 238 possible reactions, respectively, p<0.05). Interestingly, four RAO-affected but none of the control horses reacted with the recombinant mould allergen A. fumigatus 8 (rAsp f 8, p<0.05), but only late phase and delayed type reactions were observed. In all three tests the majority of the positive reactions was observed with the mite extracts (64%, 74% and 88% of all positive reactions, respectively) but none of the tests showed a significant difference between RAO-affected and control animals. Our findings do not support that IgE-mediated reactions are important in the pathogenesis of RAO. Further studies are needed to investigate whether sensitisation to mite allergens is of clinical relevance in the horse and to understand the role of immune reactions against rAsp f 8.

Strategic use of serology for the diagnosis of bovine tuberculosis after intradermal skin testing

Diagnostic tests based on cell-mediated immunity are used in programmes for eradication of bovine tuberculosis (Mycobacterium bovis). Serological assays could be applied as ancillary methods to detect infected animals. Our objective was to evaluate two serological techniques: M. bovis Ab Test (IDEXX, USA) and Enferplex™ TB assay (Enfer, Ireland) in animals tested simultaneously with the single and comparative intradermal tests and the interferon-gamma assay. This work was performed at two stages. First, a preliminary panel of samples collected prior to intradermal tests from tuberculosis-free (n=60) and M. bovis-infected herds (n=78) was assayed, obtaining high specificity: 100% (M. bovis Ab Test) and 98.3% (Enferplex TB assay) but low sensitivity (detection of M. bovis infected animals): 23.9% (M. bovis Ab Test) and 32.6% (Enferplex TB assay). Subsequently, the use of serological techniques was further studied in two herds with M. bovis infection (n=77) using samples collected prior to, and 72 h and 15 days after PPD inoculation. The highest level of detection of infected animals for serology was achieved at 15 days post-intradermal tests taking advantage of the anamnestic effect: 70.4% and 85.2% in herd A, and 66.7% and 83.3% in herd B, using M. bovis Ab Test and Enferplex TB assay, respectively. Quantitative results (average values obtained with M. bovis Ab Test ELISA and degree of positivity obtained with Enferplex TB assay) were higher in animals showing lesions compatible with tuberculosis. No significant differences were observed in the number of confirmed infected animals detected with either serological technique.

Is the lateral extension of the acromion related to the outcome of shoulder injections?

OBJECTIVE To assess patients' outcomes after subacromial or glenohumeral injections based on the degree of lateral extension of the acromion. METHODS 307 patients were prospectively included after therapeutic fluoroscopy-guided subacromial (n = 148) or glenohumeral (n = 159) injections with anaesthetic and long-acting corticosteroids. Pre- and post-injection outcomes at 1 week and 1 month were obtained using the 11-point numerical rating scale (NRS) for pain. Lateral extension of the acromion was quantified and categorized by the critical shoulder angle (CSA) and the acromion index (AI) on anteroposterior conventional radiographs. RESULTS Patients' outcomes at 1 week and 1 month were significantly improved (p < 0.001) compared to baseline for subacromial and glenohumeral injection patients. Patients with a CSA <35° showed significantly higher pain reduction 1 month after subacromial injection compared to patients with a CSA >35° (4.2 ± 2.6 vs. 3.2 ± 3.0, p = 0.04). A significant difference in the 1-month NRS change in pain scores is noted for smaller AIs after subacromial injection (4.3 ± 2.8 vs. 2.6 ± 2.9; p = 0.01). No significant association was noted between clinical outcome and the lateral extension of the acromion after glenohumeral joint injections. CONCLUSIONS A short lateral extension of the acromion was associated with better clinical outcomes in subacromial injection patients but not in glenohumeral injection patients. KEY POINTS • Patients' outcomes at 1 month improved significantly compared to baseline for subacromial injections. • Patients' outcomes at 1 month improved significantly compared to baseline for glenohumeral injections. • Short acromial lateralization was associated with better clinical outcome after subacromial injection. • The acromial lateralization was not associated with clinical outcome after glenohumeral injection.

Scleral thinning after repeated intravitreal injections of antivascular endothelial growth factor agents in the same quadrant

PURPOSE We assessed the effects of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy on scleral architecture using spectral domain anterior segment optical coherence tomography (OCT). METHODS A total of 35 eyes of 35 patients treated with at least 30 intravitreal injections in one eye in the inferotemporal quadrant with ranibizumab or aflibercept and 10 or less intravitreal injections in the fellow eye attending the intravitreal injection clinic were included. Enhanced depth imaging anterior segment OCT was used to measure scleral thickness. For each eye the sclera was measured in four quadrants at 3 mm from the limbus. In addition axial eye length was measured in all subjects using partial coherence interferometry. RESULTS The mean number of intravitreal injections was 42 (range, 30-73) and 1.6 (range, 0-9) in the fellow eyes. In the study eyes with more than 30 injections the average scleral thickness in the inferotemporal quadrant was 568.4 μm (SD ± 66 μm) and 590.6 μm (SD ± 75 μm) in the fellow eyes with 10 or less injections (P = 0.003). The mean average scleral thickness in the other three quadrants (inferonasal, superotemporal, and superonasal) was 536.6 μm in the study eyes (SD ± 100 μm) and 545.2 μm (SD ± 109 μm) in the fellow eyes (P = 0.22). There was a borderline association of the total number of injections with scleral thickness change in the inferotemporal quadrant (r = 0.3, P = 0.052). CONCLUSIONS Intravitreal injections may lead to scleral changes when applied repeatedly in the same quadrant. Thus, alternating the injection site should be considered in patients requiring multiple intravitreal injections.

Classical swine fever virus replicon particles lacking the Erns gene: a potential marker vaccine for intradermal application.

Classical swine fever virus replicon particles (CSF-VRP) deficient for E(rns) were evaluated as a non-transmissible marker vaccine. A cDNA clone of CSFV strain Alfort/187 was used to obtain a replication-competent mutant genome (replicon) lacking the sequence encoding the 227 amino acids of the glycoprotein E(rns) (A187delE(rns)). For packaging of A187delE(rns) into virus particles, porcine kidney cell lines constitutively expressing E(rns) of CSFV were established. The rescued VRP were infectious in cell culture but did not yield infectious progeny virus. Single intradermal vaccination of two pigs with 10(7) TCID(50) of VRP A187delE(rns) elicited neutralizing antibodies, anti-E2 antibodies, and cellular immune responses determined by an increase of IFN-gamma producing cells. No anti-E(rns) antibodies were detected in the vaccinees confirming that this vaccine represents a negative marker vaccine allowing differentiation between infected and vaccinated animals. The two pigs were protected against lethal challenge with the highly virulent CSFV strain Eystrup. In contrast, oral immunization resulted in only partial protection, and neither CSFV-specific antibodies nor stimulated T-cells were found before challenge. These data represent a good basis for more extended vaccination/challenge trials including larger numbers of animals as well as more thorough analysis of virus shedding using sentinel animals to monitor horizontal spread of the challenge virus.

Ranibizumab (Lucentis) in neovascular age-related macular degeneration: evidence from clinical trials

BACKGROUND: Neovascular age-related macular degeneration (AMD) has a poor prognosis if left untreated, frequently resulting in legal blindness. Ranibizumab is approved for treating neovascular AMD. However, further guidance is needed to assist ophthalmologists in clinical practice to optimise treatment outcomes. METHODS: An international retina expert panel assessed evidence available from prospective, multicentre studies evaluating different ranibizumab treatment schedules (ANCHOR, MARINA, PIER, SAILOR, SUSTAIN and EXCITE) and a literature search to generate evidence-based and consensus recommendations for treatment indication and assessment, retreatment and monitoring. RESULTS: Ranibizumab is indicated for choroidal neovascular lesions with active disease, the clinical parameters of which are outlined. Treatment initiation with three consecutive monthly injections, followed by continued monthly injections, has provided the best visual-acuity outcomes in pivotal clinical trials. If continued monthly injections are not feasible after initiation, a flexible strategy appears viable, with monthly monitoring of lesion activity recommended. Initiation regimens of fewer than three injections have not been assessed. Continuous careful monitoring with flexible retreatment may help avoid vision loss recurring. Standardised biomarkers need to be determined. CONCLUSION: Evidence-based guidelines will help to optimise treatment outcomes with ranibizumab in neovascular AMD.

In the human urothelium and suburothelium, intradetrusor botulinum neurotoxin type A does not induce apoptosis: preliminary results

Intradetrusor injections of botulinum neurotoxin type A (BoNTA) are emerging as the preferred second-line treatment for neurogenic and idiopathic overactive bladder (OAB). In animal experiments, intradetrusor BoNTA injections have been shown to cause apoptosis in the bladder urothelium and suburothelium but not the detrusor.