Intravesical aminophylline instillation as an alternative for balloon dilatation prior to semi-rigid ureteroscopic management of distal ureteral stones.

PURPOSE: In a randomized controlled trial, we evaluated the effect of intravesical aminophylline instillation (IVAI) on intraureteral pressure of lower ureter and its use as an alternative to balloon dilatation after failure of advancing semi-rigid ureteroscope through the ureteric orifice without endodilatation. METHODS: Our study included 83 patients with juxta-vesical distal ureteral calculi requiring endodilatation after unsuccessfully introducing the semi-rigid ureteroscope through the ureteric orifice. Patients were randomized into two groups: group A (study group) included 41 patients, where IVAI was used to dilate the ureter and facilitate ureteroscopy (the intraureteral pressure was measured using a pressure transducer connected to an invasive pressure monitor before and 5 min after IVAI), whereas group B (control group) included 42 patients, where balloon dilatation was used prior to ureteroscopy. Perioperative surgical outcomes of ureteroscopy were evaluated in both groups. RESULTS: A statistically significant decrease in mean intraureteral pressure of intravesical ureter was found after IVAI from 12.34 mmHg ± 1.94 before injection to 8.46 mmHg ± 1.94 after injection (P < 0.001). Ureteral injuries, postoperative pain and hematuria were statistically significantly less among the study group compared to the control group (P < 0.05). We did not find statistically significant differences in operative time, need for DJ ureteral stenting or stone-free rate between both groups and no perioperative side effects were associated with IVAI. CONCLUSION: In ureteroscopic management of distal ureteral stones, intravesical aminophylline instillation is safe, inexpensive and effective in reducing intraureteral pressure and achieves comparable outcomes to balloon dilatation with less ureteral injuries, postoperative pain and hematuria.

Extended half-life pegylated, full-length recombinant factor VIII for prophylaxis in children with severe haemophilia A.

INTRODUCTION: Primary factor VIII (FVIII) prophylaxis is the optimal treatment in children with severe haemophilia A. They are expected to benefit from extended half-life (T1/2 ) FVIII coverage by reduced infusion frequency while maintaining haemostatic efficacy. AIMS: To determine immunogenicity, pharmacokinetics (PK), efficacy, safety and quality of life of prophylaxis with a polyethylene glycol (peg)-ylated FVIII (BAX 855) based on full-length recombinant FVIII (ADVATE) in paediatric previously treated patients (PTPs) with severe haemophilia A. METHODS: PTPs <12 years without history of FVIII inhibitors received twice-weekly infusions of 50 ± 10 IU kg-1 BAX 855 for ≥50 exposure days. Prophylactic dose increases to ≤80 IU kg-1 were allowed under predefined conditions. PK was evaluated after single infusions of 60 ± 5 IU kg-1 . RESULTS: T1/2 and mean residence time were extended 1.3- to 1.5-fold compared to ADVATE (n = 31), depending on the analysis used. The point estimate for the mean annualized bleeding rate in 66 subjects receiving a median of 1.9 weekly infusions of 51.3 IU kg-1 of BAX 855 each was 3.04 (median 2.0); 1.10 (median 0) for joint and 1.16 (median 0) for spontaneous bleeds. Overall, 38% of subjects had zero bleeds. No bleeds were severe. Haemostatic efficacy was rated excellent or good for 90% of bleeds; 91% were treated with one or two infusions. In 8/14 subjects all target joints resolved. No subject developed FVIII inhibitors or persistent binding antibodies that affected safety or efficacy. No adverse reactions occurred. CONCLUSION: Twice-weekly prophylaxis with BAX 855 was safe and efficacious in paediatric PTPs with severe haemophilia A.

Building a reliable measure for unobtrusive observations of street-connecting pedestrian walkways.

There is evidence that good urban design, including street connectivity, facilitates walking for transport. We, therefore, piloted a short survey on 118 such walkways in nine suburbs in Wellington, New Zealand's capital. The instrument appeared feasible to use and performed well in terms of inter-rater reliability (median Kappa score for 15 items: 0.88). The study identified both favorable features (e.g., railings by steps), but also problematic ones (e.g., concerning graffiti, litter, and insufficient lighting and signage). There is scope for routinising the monitoring of walkway quality so that citizens and government agencies can work together to enhance urban walkability.

Utilizing combusted PET plastic waste and biogenic oils as efficient pour point depressants for crude oil.

The deposition of paraffin on pipelines during crude oil transit and low-temperature restart processes poses a significant challenge for the oil industry. Addressing this issue necessitates the exploration of innovative materials and methods. Pour point depressants (PPDs) emerge as crucial processing aids to modify paraffin crystallization and enhance crude oil flow. This study focuses on the combustion of polyethylene terephthalate (PET) waste, a prevalent plastic, in two distinct oils (castor and jatropha). The resulting black waxy substances (PET/Castor and PET/Jatropha) were introduced in varying weights (1000, 2000, and 3000 ppm) to crude oil. The PET/castor oil combination demonstrated a remarkable reduction in pour point from 18 to -21 °C at 3000 ppm concentration, significantly more effective than PET/jatropha blends. Substantial decreases in viscosity (up to 75%) and shear stress (up to 72%) were also observed for both blends, most prominently at lower temperatures near the pour point. The synergistic effect of PET and oils as nucleating agents that alter crystallization patterns and restrict crystal growth contributes to this enhanced low-temperature flow. This highlights the potential of PET plastic waste as an economical, abundant, and eco-friendly additive to develop high-performance PPDs for crude oil.

[Ethical stakes of information in radiation oncology: Thinking the risk and building the therapeutic alliance]. / Enjeux éthiques de l'information en oncologie radiothérapie : penser le risque et construire l'alliance thérapeutique.

Informing patients before receiving radiation therapy is a fundamental ethical imperative. As a condition of the possibility of autonomy, information allows people to make health decisions concerning themselves, which is required by French law. This information includes in particular the potential risks due to radiation therapy. It is therefore necessary to think about what risk is, and how to define and assess it, in order to finally communicate it. The practice of informing people involves many ethical issues relating to the very content of the information, the form in which it is transmitted or even the intention that leads the health professional to say (or not to say) the risk. The transmission of information also questions the way to build a relationship of trust with the patients and how to integrate their own representations about these treatments. Between the risks of paternalism or even defensive medicine, this practice is at the heart of our professional practice.

Zig Maneuver in Total Extraperitoneal Inguinal Hernia Repair.

BACKGROUND: The difficulties in the hernia sac dissection in repairing large inguinal hernias with the endoscopic total extraperitoneal (TEP) technique prolong the operation and increase the risk of injury. This study investigates the effectiveness of the Zig maneuver (ligation of the hernia sac at the deep inguinal ring) in TEP in male patients with L3 inguinal hernia by European Hernia Society classification. MATERIALS AND METHODS: A total of 224 male patients with L3 inguinal hernia who underwent laparoscopic TEP surgery in 2018 and 2019 were retrospectively screened and included in the study. The patients were divided into 2 groups as Zig group (n=99) and the non-Zig group (n=125), depending on whether the Zig maneuver was performed during TEP application. RESULTS: The mean patient age was 45.49 for the non-Zig group and 47.12 for the Zig group. The median operative time was 50 minutes in the non-Zig group and 43 minutes in the Zig group (P<0.005). The median value of the postoperative first 24 hours pain score was 3 in the non-Zig group and 2 in the Zig group (P=0.033). Scrotal edema was 7.2% in the non-Zig group and 1% in the Zig group (P=0.023). According to logistic regression analysis, the Zig maneuver reduced the probability of scrotal edema by 87% in almost the entire population (odds ratio=0.130, 95% confidence interval: 0.016-1.047). There was no statistically significant difference between the groups in terms of early and late recurrence. CONCLUSIONS: Zig maneuver shortened the operative time and significantly reduced the feeling of pain in the first 24 hours postoperatively in male patients with indirect L3 hernia who underwent endoscopic TEP. It also significantly reduced the likelihood of scrotal edema in almost the entire population. As a result, the Zig maneuver is an effective method that could be applied during endoscopic TEP.

The effect of patient transfer type to the operating room on surgical site infection: Concerns versus evidence.

BACKGROUND: Concerns about surgical site infection (SSI) give rise to practices and procedures not evidence-based. OBJECTIVES: This study investigates whether the type of patient transfer to operating rooms plays a role in developing surgical site infection. METHODS: Three thousand four hundred and seventy-one patients were divided into two groups: transfer group with stretcher (ST) (n = 1699) and patient bed transfer group (PBT) (n = 1772). The data of the two groups and the SSI rates were comparatively analyzed. RESULTS: The SSI rate was 2.5% (n = 43) in the ST group and 2.8% (n = 49) in the PBT group, and there was no statistically significant difference. Both types of patient transfer had similar effects on the probability of SSI development. The odds ratio was 1.095 for stretcher transfer while 0.913 for patient bed transfer. CONCLUSION: Patients transfer to operating rooms on their beds are comfortable and safe. Furthermore, it has a similar effect to stretcher transfer on the probability of surgical site infection. Therefore, it is safer and cheaper to act based on evidence instead of trusting our concerns.

ANTECEDENTES: las preocupaciones sobre la infección del sitio quirúrgico (ISQ) dan lugar a prácticas y procedimientos que no se basan en pruebas. OBJETIVOS: Este estudio investiga si el tipo de traslado del paciente a los quirófanos influye en el desarrollo de la infección del sitio quirúrgico. MÉTODOS: Se dividieron 3471 pacientes en dos grupos: Grupo de transferencia con camilla (ST) (n = 1699) y Grupo de transferencia de cama de paciente (PBT) (n = 1772). Los datos de los dos grupos y las tasas de ISQ se analizaron comparativamente. RESULTADOS: La tasa de ISQ fue de 2.5% (n = 43) en el grupo ST y 2.8% (n = 49) en el grupo PBT, y no hubo diferencia estadísticamente significativa. Ambos tipos de transferencia de pacientes tuvieron efectos similares sobre la probabilidad de desarrollo de ISQ. La razón de posibilidades fue de 1.095 para el traslado en camilla y de 0,913 para el traslado de la cama del paciente. CONCLUSIÓN: El traslado de los pacientes a los quirófanos en sus camas es cómodo y seguro. Además, tiene un efecto similar al traslado en camilla sobre la probabilidad de infección del sitio quirúrgico. Por lo tanto, es más seguro y económico actuar en base a evidencias en lugar de confiar en nuestras preocupaciones.

Vaccines to prevent pneumonia and improve child survival.

For more than 30 years, vaccines have played an important part in pneumonia prevention. Recent advances have created opportunities for further improving child survival through prevention of childhood pneumonia by vaccination. Maximizing routine immunization with pertussis and measles vaccines, coupled with provision of a second opportunity for measles immunization, has rapidly reduced childhood deaths in low-income countries especially in sub-Saharan Africa. Vaccines against the two leading bacterial causes of child pneumonia deaths, Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae (pneumococcus), can further improve child survival by preventing about 1,075,000 child deaths per year. Both Hib and pneumococcal conjugate vaccines have proven safety and effectiveness for prevention of radiologically confirmed pneumonia in children, including in low-income and industrializing countries. Both are recommended by WHO for inclusion in national programmes, and, at sharply tiered prices, these vaccines generally meet international criteria of cost-effectiveness for low-income countries. Vaccines only target selected pneumonia pathogens and are less than 100% effective, so they must be complemented by curative care and other preventative strategies. As part of a comprehensive child survival package, the particular advantages of vaccines include the ability to reach a high proportion of all children, including those who are difficult to reach with curative health services, and the ability to rapidly scale up coverage with new vaccines. In this review, we discuss advances made in optimizing the use of established vaccines and the potential issues related to newer bacterial conjugate vaccines in reducing childhood pneumonia morbidity and mortality.

Economic evaluation of border closure for a generic severe pandemic threat using New Zealand Treasury methods.

OBJECTIVE: To perform a comprehensive economic evaluation of border closure for an island nation in the face of severe pandemic scenarios. METHODS: The costing tool developed by the New Zealand (NZ) Treasury (CBAx) was used for the analyses. Pandemic scenarios were as per previous work;1 epidemiological data were from past New Zealand influenza pandemics. RESULTS: The net present value of successful border closure was NZ$7.86 billion for Scenario A (half the mortality rate of the 1918 influenza pandemic) and $144 billion for preventing a more severe pandemic (10 times the mortality of scenario A). Cost-utility analyses found border closure was relatively cost-effective, at $14,400 per QALY gained in Scenario A, and cost-saving for Scenario B (taking the societal perspective). CONCLUSIONS: This work quantifies the economic benefits and costs from border closure for New Zealand under specific assumptions in a generic but severe pandemic threat (e.g. influenza, synthetic bioweapon). Preparing for such a pandemic response seems wise for an island nation, although successful border closure may only be feasible if planned well ahead. Implications for public health: Policy makers responsible for generic pandemic planning should explore how border closure could be implemented, including practical and legal frameworks.

"Mycobacterium massilipolynesiensis" sp. nov., a rapidly-growing mycobacterium of medical interest related to Mycobacterium phlei.

In French Polynesia, respiratory tract clinical isolate M26, displayed unusual phenotype and contradictory phylogenetic affiliations, suggesting a hitherto unidentified rapidly-growing Mycobacterium species. The phenotype of strain M26 was further characterized and its genome sequenced. Strain M26 genome consists in a 5,732,017-bp circular chromosome with a G + C% of 67.54%, comprising 5,500 protein-coding genes and 52 RNA genes (including two copies of the 16 S rRNA gene). One region coding for a putative prophage was also predicted. An intriguing characteristic of strain M26's genome is the large number of genes encoding polyketide synthases and nonribosomal peptide synthases. Phylogenomic analysis showed that strain M26's genome is closest to the Mycobacterium phlei genome with a 76.6% average nucleotide identity. Comparative genomics of 33 Mycobacterium genomes yielded 361 genes unique to M26 strain which functional annotation revealed 84.21% of unknown function and 3.88% encoding lipid transport and metabolism; while 48.87% of genes absent in M26 strain have unknown function, 9.5% are implicated in transcription and 19% are implicated in transport and metabolism. Strain M26's unique phenotypic and genomic characteristics indicate it is representative of a new species named "Mycobacterium massilipolynesiensis". Looking for mycobacteria in remote areas allows for the discovery of new Mycobacterium species.

Protecting an island nation from extreme pandemic threats: Proof-of-concept around border closure as an intervention.

BACKGROUND: Countries are well advised to prepare for future pandemic risks (e.g., pandemic influenza, novel emerging agents or synthetic bioweapons). These preparations do not typically include planning for complete border closure. Even though border closure may not be instituted in time, and can fail, there might still plausible chances of success for well organized island nations. OBJECTIVE: To estimate costs and benefits of complete border closure in response to new pandemic threats, at an initial proof-of-concept level. New Zealand was used as a case-study for an island country. METHODS: An Excel spreadsheet model was developed to estimate costs and benefits. Case-study specific epidemiological data was sourced from past influenza pandemics. Country-specific healthcare cost data, valuation of life, and lost tourism revenue were imputed (with lost trade also in scenario analyses). RESULTS: For a new pandemic equivalent to the 1918 influenza pandemic (albeit with half the mortality rate, "Scenario A"), it was estimated that successful border closure for 26 weeks provided a net societal benefit (e.g., of NZ$11.0 billion, USD$7.3 billion). Even in the face of a complete end to trade, a net benefit was estimated for scenarios where the mortality rate was high (e.g., at 10 times the mortality impact of "Scenario A", or 2.75% of the country's population dying) giving a net benefit of NZ$54 billion (USD$36 billion). But for some other pandemic scenarios where trade ceased, border closure resulted in a net negative societal value (e.g., for "Scenario A" times three for 26 weeks of border closure-but not for only 12 weeks of closure when it would still be beneficial). CONCLUSIONS: This "proof-of-concept" work indicates that more detailed cost-benefit analysis of border closure in very severe pandemic situations for some island nations is probably warranted, as this course of action might sometimes be worthwhile from a societal perspective.

What's new with the flu? Reflections regarding the management and prevention of influenza from the 2nd New Zealand Influenza Symposium, November 2015.

Influenza is a common respiratory viral infection. Seasonal outbreaks of influenza cause substantial morbidity and mortality that burdens healthcare services every year. The influenza virus constantly evolves by antigenic drift and occasionally by antigenic shift, making this disease particularly challenging to manage and prevent. As influenza viruses cause seasonal outbreaks and also have the ability to cause pandemics leading to widespread social and economic losses, focused discussions on improving management and prevention efforts is warranted. The Immunisation Advisory Centre (IMAC) hosted the 2nd New Zealand Influenza Symposium (NZiS) in November 2015. International and national participants discussed current issues in influenza management and prevention. Experts in the field presented data from recent studies and discussed the ecology of influenza viruses, epidemiology of influenza, methods of prevention and minimisation, and experiences from the 2015 seasonal influenza immunisation campaign. The symposium concluded that although much progress in this field has been made, many areas for future research remain.

Evaluation of technical factors affecting the quantification of trabecular bone structure using magnetic resonance imaging.

High resolution magnetic resonance (MR) techniques combined with standard techniques of stereology and texture analysis have been used to quantify trabecular structure. Using dried excised specimens from the tibia (n = 10) and radius (n = 2) we evaluate the impact of using volumetric gradient-echo (GE) and spin-echo (SE) MR imaging sequences, the relative importance of echo time in gradient-echo MR imaging, and the impact of different threshold values to segment the bone and bone marrow on the estimation of trabecular bone structure. We also investigate the inter-relationships between the different structural parameters derived from MR images. Images were obtained using fast gradient-echo and spin-echo imaging sequences, with TE values ranging from 7 to 17 ms using 4.7 and 1.5 Tesla imaging systems. In-plane image resolution ranged from 128 to 156 microns, and slice thickness ranged from 128 to 1000 microns. We derived stereological measures such as the mean intercept length, trabecular width, fractional area of trabecular bone, trabecular number, and trabecular spacing, the fractal dimension as a texture-related parameter and the Euler number as a measure of connectivity from these images. We found that the mean intercept length as a function of angle traced an ellipse with the orientation of the principal axis of the ellipse, a measure of trabecular orientation, identical when measured from the spin-echo or gradient-echo MR images. Absolute measures such as the fractional area, trabecular width, trabecular number, and fractal dimension as measured from gradient echo images were 28%, 30%, 1.3%, and 0.6% greater, respectively, than those calculated from spin-echo images, while the trabecular spacing was 14% less when calculated from gradient-echo images compared to spin-echo images. The structural parameters also depended on the echo time used to obtain the MR image. The choice of the threshold used to segment the high resolution images also affected the estimated structural parameters significantly. Our results indicate that MR may be used to visualize and quantify trabecular bone architecture; however, the different technical factors that could affect the appearance of MR images must be understood and considered in the data analysis and interpretation.

Administration of a small molecule tissue factor/factor VIIa inhibitor in a non-human primate thrombosis model of venous thrombosis: effects on thrombus formation and bleeding time.

INTRODUCTION: Pharmacological treatment of deep vein thrombosis (DVT) in the future may target inhibitors of specific procoagulant proteins. This study used a non-human primate model to test the effect of PHA-798, a specific inhibitor of the tissue factor/Factor VIIa complex (TF/VIIa), on venous thrombus formation. MATERIALS AND METHODS: PHA inhibits the TF/VIIa complex with an IC(50) of 13.5 nM (K(i) 9 nM) and is more than 2000-fold selective for the TF/VIIa complex with respect to IC(50)s for factor Xa and thrombin. In the model, a thrombogenic surface was introduced into the vena cava of a primate, and the amount of thrombus accumulated after 30 min was determined. RESULTS: PHA-798 reduced thrombus formation on the thrombogenic surface in a dose-dependent manner (56+/-1.9% and 85+/-0.3% inhibition with 100 and 200 microg/kg/min PHA-798, respectively) indicating that the model is sensitive to TF/VIIa inhibition. Treatment with 1 mg/kg intravenous (IV) acetyl salicylic acid (ASA) resulted in only a slight (4-12%), non-significant inhibition of thrombus formation. However, the combination of 100 microg/kg/min PHA-798 and 1 mg/kg ASA resulted in an 89% inhibition of thrombus formation. Additionally, while ASA alone increased bleeding time (BT) from 3.3 min at baseline to 4.6 min following treatment, addition of PHA-798 (100 microg/kg/min) to ASA did not significantly increase the BT further (4.7 min). CONCLUSIONS: The results of this study indicate that inhibition of TF/VIIa may be safe and effective for the prevention of the proprogation of venous thrombosis and that the combination of ASA and PHA may provide increased efficacy with little change in safety.

[Paragonimiasis: a rare little known disease]. / La paragonimose: une affection rare à ne pas méconnaître.

BACKGROUND: Paragonimiasis, caused by a lung fluke, is an parasitic disease rarely encountered in France. CASE REPORT: A 52-year-old man developed dyspnea, cough, mild fever and chest pain. Pleural effusion suggested possible pulmonary embolism or tuberculosis. Cell counts in blood and pleural effusion fluid revealed major eosinophila in this patient who had recently returned from a trip to Japan. Paragonimiasis was confirmed by ELISA. Treatment with praziquantel led to complete clinical and radiographic recovery. DISCUSSION: The clinical and radiographic features of paragonimiasis are often similar to tuberculosis with pleuropneumopathy, mild fever and dyspnea. ELISA has now replaced parasitologic diagnosis. Cure is achieved with praziquantel.

Pontin is a critical regulator for AML1-ETO-induced leukemia.

The oncogenic fusion protein AML1-ETO, also known as RUNX1-RUNX1T1 is generated by the t(8;21)(q22;q22) translocation, one of the most frequent chromosomal rearrangements in acute myeloid leukemia (AML). Identifying the genes that cooperate with or are required for the oncogenic activity of this chimeric transcription factor remains a major challenge. Our previous studies showed that Drosophila provides a genuine model to study how AML1-ETO promotes leukemia. Here, using an in vivo RNA interference screen for suppressors of AML1-ETO activity, we identified pontin/RUVBL1 as a gene required for AML1-ETO-induced lethality and blood cell proliferation in Drosophila. We further show that PONTIN inhibition strongly impaired the growth of human t(8;21)(+) or AML1-ETO-expressing leukemic blood cells. Interestingly, AML1-ETO promoted the transcription of PONTIN. Moreover, transcriptome analysis in Kasumi-1 cells revealed a strong correlation between PONTIN and AML1-ETO gene signatures and demonstrated that PONTIN chiefly regulated the expression of genes implicated in cell cycle progression. Concordantly, PONTIN depletion inhibited leukemic self-renewal and caused cell cycle arrest. All together our data suggest that the upregulation of PONTIN by AML1-ETO participate in the oncogenic growth of t(8;21) cells.

The use of dynamic mechanical analysis (DMA) to evaluate plasticization of acrylic polymer films under simulated gastrointestinal conditions.

PURPOSE: Glass transition temperature (T(g)) measurements of polymers are conventionally conducted in the dry state with little attention to the environment they are designed to work in. Our aim was to develop the novel use of dynamic mechanical analysis (DMA) to measure the T(g) of enteric polymethacrylic acid methylmethacrylate (Eudragit L and S) polymer films formulated with a range of plasticizers in the dry and wet (while immersed in simulated gastric media) states. METHODS: Polymer films were fabricated with and without different plasticizers (triacetin, acetyl triethyl citrate, triethyl citrate, polyethylene glycol, propylene glycol, dibutyl phthalate, dibutyl sebacate). T(g) was measured by a dynamic oscillating force with simultaneous heating at 1 °C/min. This was conducted on films in the dry state and while immersed in 0.1M HCl to simulate the pH environment in the stomach. RESULTS: The T(g) of unplasticized Eudragit L and S films in the dry state was measured to be 150 and 120 °C, respectively. These values were drastically reduced in the wet state to 20 and 71 °C for Eudragit L and S films, respectively. The plasticized films showed similar falls in T(g) in the wet state. The fall in T(g) of Eudragit L films to below body temperature will have far-reaching implications on polymer functionality and drug release. CONCLUSIONS: Immersion DMA provides a robust method for measuring T(g) of polymer films in the wet state. This allows better prediction of polymer behaviour in vivo.