Evaluating newly approved drugs in combination regimens for multidrug-resistant tuberculosis with fluoroquinolone resistance (endTB-Q): study protocol for a multi-country randomized controlled trial.

BACKGROUND: Treatment for fluoroquinolone-resistant multidrug-resistant/rifampicin-resistant tuberculosis (pre-XDR TB) often lasts longer than treatment for less resistant strains, yields worse efficacy results, and causes substantial toxicity. The newer anti-tuberculosis drugs, bedaquiline and delamanid, and repurposed drugs clofazimine and linezolid, show great promise for combination in shorter, less-toxic, and effective regimens. To date, there has been no randomized, internally and concurrently controlled trial of a shorter, all-oral regimen comprising these newer and repurposed drugs sufficiently powered to produce results for pre-XDR TB patients. METHODS: endTB-Q is a phase III, multi-country, randomized, controlled, parallel, open-label clinical trial evaluating the efficacy and safety of a treatment strategy for patients with pre-XDR TB. Study participants are randomized 2:1 to experimental or control arms, respectively. The experimental arm contains bedaquiline, linezolid, clofazimine, and delamanid. The control comprises the contemporaneous WHO standard of care for pre-XDR TB. Experimental arm duration is determined by a composite of smear microscopy and chest radiographic imaging at baseline and re-evaluated at 6 months using sputum culture results: participants with less extensive disease receive 6 months and participants with more extensive disease receive 9 months of treatment. Randomization is stratified by country and by participant extent-of-TB-disease phenotype defined according to screening/baseline characteristics. Study participation lasts up to 104 weeks post randomization. The primary objective is to assess whether the efficacy of experimental regimens at 73 weeks is non-inferior to that of the control. A sample size of 324 participants across 2 arms affords at least 80% power to show the non-inferiority, with a one-sided alpha of 0.025 and a non-inferiority margin of 12%, against the control in both modified intention-to-treat and per-protocol populations. DISCUSSION: This internally controlled study of shortened treatment for pre-XDR TB will provide urgently needed data and evidence for clinical and policy decision-making around the treatment of pre-XDR TB with a four-drug, all-oral, shortened regimen. TRIAL REGISTRATION: ClinicalTrials.Gov NCT03896685. Registered on 1 April 2018; the record was last updated for study protocol version 4.3 on 17 March 2023.

Novel adsorbent based on carbon-modified zirconia/spinel ferrite nanostructures: Evaluation for the removal of cobalt and europium radionuclides from aqueous solutions.

Herein, a novel adsorbent based on carbon-modified zirconia/spinel ferrite (C@ ZrO2/Mn0.5Mg0.25Zn0.25Fe2O4) nanostructures were chemically prepared to remove 60Co and 152+154Eu radionuclides from liquid media using batch experiments. The XRD pattern confirms the successful preparation of the C@ZrO2/MnMgZnFe2O4 composite. Also, SEM and TEM images confirmed that the composite owns a heterogeneous morphology in the nanoscale range. The optical band gap value of Mn0.5Mg0.25Zn0.25Fe2O4, ZrO2, and the composite samples was 1.45, 2.38, and 1.54 eV, respectively. Many parameters have been studied as the effect of time, solution pH, and initial ion concentration. The kinetics models for the removal process of 152+154Eu and 60Co radionuclides were studied. The second-order kinetic equation could describe the sorption kinetics for both radionuclides. The Langmuir monolayer capacity for 60Co was 82.51 mg/g and for 152+154Eu was 136.98 mg/g. The thermodynamic parameters such as free energy ΔGo, the enthalpy ΔHo, and the entropy ΔSo were calculated. The results indicated that the sorption process has endothermic nature for both two radionuclides onto C@ZrO2/MnMgZnFe2O4 composite.

Prevalence and antimicrobial resistance pattern of multidrug-resistant enterococci isolated from clinical specimens.

PURPOSE: Vancomycin-resistant enterococci (VRE) pose an emerging problem in hospitals worldwide. The present study was undertaken to determine the occurrence, species prevalence, antibacterial resistance, and phenotypic and genetic characteristics of VRE isolated in Riyadh hospitals, KSA. MATERIALS AND METHODS: Two hundred and six isolates of enterococcal species were obtained from clinical samples. The antibiotic susceptibility of isolates and minimum inhibitory concentration (MIC) tests for vancomycin and teicoplanin were determined. Molecular typing of VRE isolates was carried out by using pulsed field gel electrophoresis (PFGE) and the resistance genotype was determined by polymerase chain reaction (PCR). RESULTS: VRE accounted for 3.9% of the isolates and were detected mostly in urine, wound and blood specimens isolated from ICU, internal medicine and surgical wards. All strains were identified to species level and were found to consist of E. faecalis (69.2%), E. faecium (11.3%), E. avium (2.1%), E. hirae (0.8%), E. casseliflavus (1.3%) and E. gallinarum (1.3%) species. According to the susceptibility data obtained, 8 (3.9%) out of 206 isolates were found to be VRE (MICs > 32 µg/ml). The vanA, vanB and vanC gene fragments of E. faecalis, E. faecium and E. gallinarum were amplified from isolates and were detected. PFGE patterns of the VRE isolates revealed homogenous patterns with dominant clone suggesting that the strains intrinsic resistance is independent. CONCLUSIONS: This study shows an emergence of VRE along with increased rate of multidrug-resistant enterococci in the area of the study. Regular surveillance of antimicrobial susceptibilities should be done regularly and the risk factors should be determined.

In utero treatment of severe fetal anaemia due to parvovirus B19 in one fetus in a twin pregnancy--a case report and literature review.

BACKGROUND: Parvovirus B19 (PVB19) is a well-established cause of nonimmune hydrops fetalis and fetal anaemia in pregnancy. However, discordant viral infection of only 1 fetus in a twin pregnancy is a rare occurrence. CASE REPORT: A 40-year-old female with dichorionic, diamniotic twin pregnancy presented at 22 weeks with fetal hydrops and severe anaemia in 1 twin. Maternal PVB19 infection was confirmed, and the affected fetus was treated with a single intrauterine transfusion. The only subsequent complication developed was that the affected fetus was growing on the 5th centile. The affected twin continued to grow, and 2 live twins were delivered by caesarean section at 36 weeks. By 18 months of age, the affected twin had normal development. CONCLUSION: PVB19 may selectively affect 1 fetus in a dichorionic, diamniotic twin pregnancy and may be treated efficiently with intrauterine transfusion. Discordant viral infection in this case suggests that the viral load may be limited to 1 placenta and/or that different individual immunological fetal response starts very early in utero.

Risk factors for anal sphincter disruption during child birth.

BACKGROUND AND AIMS: The objective of our study was to analyse the risk factors in a cohort of women who suffered anal sphincter disruption (third-degree tear) and compare the results with a similar cohort of women who underwent an uncomplicated vaginal delivery (without a clinically detectable laceration) during the same period. MATERIALS AND METHODS: A retrospective analysis was carried out on 54 women (group 1) who suffered a third-degree tear and 71 women who had undergone uncomplicated vaginal delivery during the same period (group 2). The risk factors considered were forceps delivery, parity, second stage of labour longer than 1 h, episiotomy, birth weight over 4 kg, gestational age and maternal age at delivery. The Cleveland Incontinence Score was completed. RESULTS: Multiple logistic regression analysis of obstetric risk factors for third-degree perineal tear indicated forceps delivery (p = 0.0001), primiparity (p = 0.004), foetal birth weight over 4 kg (p = 0.030) and delay in the second stage of labour (p = 0.031) to be significant risk factors for a third-degree tear. Mediolateral episiotomy was shown to be a significant protective factor (p = 0.0001). Gestational age and the maternal age at delivery (p = 0.340) were not shown to be significant risk factors (p = 0.336). CONCLUSION: Primary prevention and identification of women with risk factors is recommended. In some cases, counselling regarding the potential risks and benefits of both vaginal and caesarean delivery may be appropriate.

Long-term anal continence and quality of life following postpartum anal sphincter injury.

OBJECTIVE: Anal incontinence occurs as a result of damage to pelvic floor and the anal sphincter. In women, vaginal delivery has been recognized as the primary cause. To date, figures quoted for overt third degree anal sphincter tear vary between 0% and 26.9% of all vaginal deliveries and the prevalence of anal incontinence following primary repair vary between 15% and 61%. Our aim was to analyse the long-term (minimum 10 years post primary repair) anorectal function and quality of life in a cohort of women who suffered a third degree tear (Group 1) and compare the results with a cohort of women who underwent an uncomplicated vaginal delivery (Group 2) or an elective caesarean delivery (Group 3). METHOD: In all, 107 patients who suffered a third degree tear between 1981 and 1993 were contacted with a validated questionnaire. The two control groups comprised of 125 patients in each category. Those who responded to the questionnaire were invited for anorectal physiology studies and endoanal ultrasound. RESULTS: Of the total number contacted, 54, 71 and 54 women from the three groups returned the completed questionnaire. In the three groups, a total of 28 (53%), 13 (19%) and six (11%) complained of anal incontinence (P < 0.0001) respectively. Comparison of quality of life scores between the groups showed a poorer quality of life in those who suffered a tear (P < 0.0001). In addition, in spite of primary repair, 13 (59%) patients in group 1 showed a persistent sphincter defect compared to one (4%) occult defect in Group 2 and none in Group 3. CONCLUSION: Our study indicates that long-term results of primary repair are not encouraging. It therefore emphasizes the importance of primary prevention and preventing further sphincter damage in those who have already suffered an injury (during subsequent deliveries).