Investigation of crystal structure formation by electropulse treatment of amorphous Ti50Ni25Cu25 alloy ribbons

The study of the effect of electropulse treatment with a variable duration on the crystallization processes and the structure of a amorphous TiNiCu alloy with 25 at.% Cu in comparison with isothermal annealing and heating at a constant speed was carried out. The alloy was fabricated by rapid-quenching from the liquid state (melt spinning technique) at the cooling rate of the melt of about 106 °C/s in the form of a ribbon with a thickness of 28 μm with a surface crystal layer with a thickness of about 2-3 μm. To remove the crystal layer, the method of double-sided electrochemical polishing was used. The studies were carried out by methods of differential scanning calorimetry, metallography and scanning electron microscopy. It was established that the formation of the crystalline phase in the electropulse treatment of the amorphous ribbon occurs from the surface to the inner part due to the predominant formation and growth of columnar crystals with subsequent nucleation and growth of crystals in the rest of the ribbon.

RAID Prediction: Pilot Study of Fecal Microbial Signature With Capacity to Predict Response to Anti-TNF Treatment

Background and Aims Crohn’s disease and ulcerative colitis evolve with alternate outbreaks and remissions of variable duration in both cases. Despite the advances, about 10-30% of patients do not respond to the treatment after the induction period. Besides, between 20% to 50% further patients need an optimization of the dose to respond the treatment. Recent studies have pointed gut microbiota can play a role in the anti-TNF treatment response. This study aimed to define a bacterial signature that could be used to predict the response of patients to anti-TNF treatment. Methods There were obtained 38 stool samples from 38 IBD patients before starting anti-TNF treatments: Adalimumab, Golimumab or Infliximab. Patients were differentiated in 2 groups: responders and non-responders to biological treatment. From each sample, DNA was purified and used in a qPCR for the quantification of the 8 microbial markers. Results In this proof of concept, the predictive ability to identify anti-TNF treatment responders was analyzed. An algorithm consisting in the combination of 4 bacterial markers showed a high capacity to discriminate between responders and non- responders. The algorithm proved high sensitivity and specificity reporting values of 93.33% and 100% respectively, with a positive predictive value of 100% and a negative predictive value of 75% for predicting response to biologic treatment. Conclusions A specific bacterial signature could beneficiate patients with inflammatory bowel disease predicting the therapeutic effectiveness of an anti-TNF treatment, leading to a personalized therapy, improving the patients’ quality of life, saving costs and gaining time in patient improvement.

Spondylodiscitis due to Salmonella Typhi: a series of four cases

ABSTRACT Salmonella Typhi is very rarely associated with focal bone and joint complications. Classically, they are described in patients with risk factors such as haemoglobinopathies. We report four cases of spondylodiscitis, where the aetiology was found to be Salmonella Typhi. All four cases were treated successfully with variable duration of ceftriaxone followed by cotrimoxazole. We report these cases to highlight the importance of obtaining a microbiological diagnosis and the possibility of a rare infection in endemic settings.

Analysis of Flow Characteristics and Paracetamol Tablet Hardness Using 2D Double Mixer of Design Drum Type with Rotation and Mixing Time Variations

One of the tablet manufacturing processes using the wet granulation method is the process of mixing the active ingredient granules, fillers, binders and pelicans. The parameters of the mixing process are important to study because they will affect the physical properties of the tablet. This study studied the effect of the variable duration and the size of the mixing cycle on the physical properties of paracetamol tablets using a 2D double mixer. The results of the analysis and testing showed that the variation of mixing time and the size of the rotation had a significant effect on the flow properties of the granules and the hardness of the tablets. In addition, the optimal parameter results to obtain optimal tablet hardness occurred at 15 minutes of mixing process and 50 rpm of rotation.

Variable short duration treatment versus standard treatment, with and without adjunctive ribavirin, for chronic hepatitis C: the STOP-HCV-1 non-inferiority, factorial RCT

Background High cure rates with licensed durations of therapy for chronic hepatitis C virus suggest that many patients are overtreated. New strategies in individuals who find it challenging to adhere to standard treatment courses could significantly contribute to the elimination agenda. Objectives To compare cure rates using variable ultrashort first-line treatment stratified by baseline viral load followed by retreatment, with a fixed 8-week first-line treatment with retreatment with or without adjunctive ribavirin. Design An open-label, multicentre, factorial randomised controlled trial. Randomisation Randomisation was computer generated, with patients allocated in a 1 : 1 ratio using a factorial design to each of biomarker-stratified variable ultrashort strategy or fixed duration and adjunctive ribavirin (or not), using a minimisation algorithm with a probabilistic element. Setting NHS. Participants A total of 202 adults (aged ≥ 18 years) infected with chronic hepatitis C virus genotype 1a/1b or 4 for ≥ 6 months, with a detectable plasma hepatitis C viral load and no significant fibrosis [FibroScan® (Echosens, Paris, France) score F0–F1 or biopsy-proven minimal fibrosis], a hepatitis C virus viral load < 10,000,000 IU/ml, no previous exposure to direct-acting antiviral therapy for this infection and not pregnant. Patients co-infected with human immunodeficiency virus were eligible if human immunodeficiency virus viral load had been < 50 copies/ml for > 24 weeks on anti-human immunodeficiency virus drugs. Interventions Fixed-duration 8-week first-line therapy compared with variable ultrashort first-line therapy, initially for 4–6 weeks (continuous scale) stratified by screening viral load (variable ultrashort strategy 1, mean 32 days of treatment) and then, subsequently, for 4–7 weeks (variable ultrashort strategy 2 mean 39 days of duration), predominantly with ombitasvir, paritaprevir, ritonavir (Viekirax®; AbbVie, Chicago, IL, USA), and dasabuvir (Exviera®; AbbVie, Chicago, IL, USA) or ritonavir. All patients in whom first-line treatment was unsuccessful were immediately retreated with 12 weeks’ sofosbuvir, ledipasvir (Harvoni®, Gilead Sciences, Inc., Foster City, CA, USA) and ribavirin. Main outcome measure The primary outcome was overall sustained virological response (persistently undetectable) 12 weeks after the end of therapy (SVR12). Results A total of 202 patients were analysed. All patients in whom the primary outcome was evaluable achieved SVR12 overall [100% (197/197), 95% confidence interval 86% to 100%], demonstrating non-inferiority between fixed- and variable-duration strategies (difference 0%, 95% confidence interval –3.8% to 3.7%, prespecified non-inferiority margin 4%). A SVR12 following first-line treatment was achieved in 91% (92/101; 95% confidence interval 86% to 97%) of participants randomised to the fixed-duration strategy and by 48% (47/98; 95% confidence interval 39% to 57%) allocated to the variable-duration strategy. However, the proportion achieving SVR12 was significantly higher among those allocated to variable ultrashort strategy 2 [72% (23/32), 95% confidence interval 56% to 87%] than among those allocated to variable ultrashort strategy 1 [36% (24/66), 95% confidence interval 25% to 48%]. Overall, a SVR12 following first-line treatment was achieved by 72% (70/101) (95% confidence interval 65% to 78%) of patients treated with ribavirin and by 68% (69/98) (95% confidence interval 61% to 76%) of those not treated with ribavirin. A SVR12 with variable ultrashort strategies 1 and 2 was 52% (25/48) (95% confidence interval 38% to 65%) with ribavirin, compared with 44% (22/50) (95% confidence interval 31% to 56) without. However, at treatment failure, the emergence of viral resistance was lower with ribavirin [12% (3/26), 95% confidence interval 2% to 30%] than without [38% (11/29), 95% confidence interval 21% to 58%; p = 0.01]. All 10 individuals who became undetectable at day 3 of treatment achieved first-line SVR12 regardless of treatment duration. Five participants in the variable-duration arm and five in the fixed-duration arm experienced serious adverse events (p = 0.69), as did five participants receiving ribavirin and five participants receiving no ribavirin. Conclusions SVR12 rates were significantly higher when ultrashort treatment varied between 4 and 7 weeks, rather than between 4 and 6 weeks. We found no evidence of ribavirin significantly affecting first-line SVR12, with unsuccessful first-line short-course therapy also not compromising subsequent retreatment with sofosbuvir, ledipasvir and ribavirin. Future work A priority for future work needs to be the development and evaluation of robust predictive measures to identify those patients who can be cured with ultrashort courses of therapy. Trial registration Current Controlled Trials ISRCTN37915093, EudraCT 2015-005004-28 and CTA 19174/0370/001-0001. Funding This project was funded by the Efficacy and Mechanism Evaluation programme, a MRC and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 8, No. 17. See the NIHR Journals Library website for further project information.

Variable Duration of Viral Shedding in Cancer Patients with COVID-19

In this retrospective study of 105 SARS COV-2 infected cancer patients with longitudinal nasopharyngeal sampling, the duration of viral shedding and time to attain cycle threshold >30 was longer in patients with hematologic malignancy than those with solid tumors. These findings have important public health implications.

Strategic treatment optimization for HCV (STOPHCV1): a randomised controlled trial of ultrashort duration therapy for chronic hepatitis C

Background: The World Health Organization (WHO) has identified the need for a better understanding of which patients with hepatitis C virus (HCV) can be cured with ultrashort course HCV therapy. Methods: A total of 202 individuals with chronic HCV were randomised to fixed-duration shortened therapy (8 weeks) vs variable-duration ultrashort strategies (VUS1/2). Participants not cured following first-line treatment were retreated with 12 weeks’ sofosbuvir/ledipasvir/ribavirin. The primary outcome was sustained virological response 12 weeks (SVR12) after first-line treatment and retreatment. Participants were factorially randomised to receive ribavirin with first-line treatment. Results: All evaluable participants achieved SVR12 overall (197/197, 100% [95% CI 98-100]) demonstrating non-inferiority between fixed-duration and variable-duration strategies (difference 0% [95% CI -3.8%, +3.7%], 4% pre-specified non-inferiority margin). First-line SVR12 was 91% [86%-97%] (92/101) for fixed-duration vs 48% [39%-57%] (47/98) for variable-duration, but was significantly higher for VUS2 (72% [56%-87%] (23/32)) than VUS1 (36% [25%-48%] (24/66)). Overall, first-line SVR12 was 72% [65%-78%] (70/101) without ribavirin and 68% [61%-76%] (69/98) with ribavirin (p=0.48). At treatment failure, the emergence of viral resistance was lower with ribavirin (12% [2%-30%] (3/26)) than without (38% [21%-58%] (11/29), p=0.01). Conclusions: Unsuccessful first-line short-course therapy did not compromise retreatment with sofosbuvir/ledipasvir/ribavirin (100% SVR12). SVR12 rates were significantly increased when ultrashort treatment varied between 4-7 weeks rather than 4-6 weeks. Ribavirin significantly reduced resistance emergence in those failing first-line therapy. ISRCTN Registration: 37915093 (11/04/2016).

Antibiotic prophylaxis in cesarean sections: a tertiary care hospital based survey

Background: The objective of the study was to study the pattern of prophylactic antibiotics usage in caesarean sections in Indian settings.Methods: A cross-sectional observational study was done on women undergoing elective and emergency caesarean sections in the Department of obstetrics and gynecology who were given antibiotics according to the existing trends in the hospital.Results: Almost 72% women received prophylactic antibiotics within 30-60 minutes of skin incision while rest 28% received it before 60 minutes. In post-operative period around 80% of the women received injectable antibiotics for 48 hours, 12% for 72 hours and rest 8% received antibiotics for more than 72 hours. 90% of the patients received injections ceftriaxone 1 gm IV BD, gentamycin 80 mg IV BD metronidazole 400 mg iv TDS while 10% received injection Ampicillin 500 mg QID along with Injection Metronidazole 400 mg iv TDS and injection gentamycin 80 mg IV BD. Two percent of the cases developed wound sepsis and required change to higher antibiotics.Conclusions: In spite of recommendations by International Guidelines for single dose of prophylactic antibiotics, multiple doses are being given. There are no Indian guidelines for antibiotic prophylaxis in cesarean sections and as a result, various combinations of antibiotics are being given for variable duration leading to antibiotic resistance and increased cost of treatment.

Analgesia, Sedation, and Neuromuscular Blockade in Infants with Congenital Diaphragmatic Hernia

Objective The aim of this study was to describe the use, duration, and intercenter variation of analgesia and sedation in infants with congenital diaphragmatic hernia (CDH). Study Design This is a retrospective analysis of analgesia, sedation, and neuromuscular blockade use in neonates with CDH. Patient data from 2010 to 2016 were abstracted from the Children's Hospitals Neonatal Database and linked to the Pediatric Health Information System. Patients were excluded if they also had non-CDH conditions likely to affect the use of the study medications. Results A total of 1,063 patients were identified, 81% survived, and 30% were treated with extracorporeal membrane oxygenation (ECMO). Opioid (99.8%), sedative (93.4%), and neuromuscular blockade (87.9%) use was common. Frequency of use was higher and duration was longer among CDH patients treated with ECMO. Unadjusted duration of use varied 5.6-fold for benzodiazepines (median: 14 days) and 7.4-fold for opioids (median: 16 days). Risk-adjusted duration of use varied among centers, and prolonged use of both opioids and benzodiazepines ≥5 days was associated with increased mortality (p < 0.001) and longer length of stay (p < 0.001). Use of sedation or neuromuscular blockade prior to or after surgery was each associated with increased mortality (p ≤ 0.01). Conclusion Opioids, sedatives, and neuromuscular blockade were used commonly in infants with CDH with variable duration across centers. Prolonged combined use ≥5 days is associated with mortality. Key Points