Nasal Carriage and Antimicrobial Susceptibility of Staphylococcus aureus in healthy preschool children in Ujjain, India

<p>Abstract</p> <p>Background</p> <p>There is increasing evidence that community acquired <it>S. aureus </it>infections are spreading among healthy children. Nasal colonization with <it>S. aureus </it>plays pivotal role in the increasing prevalence of resistant community acquired <it>S. aureus </it>infections worldwide. A regular surveillance system is important in ensuring quality of patient care. The aim of the study was to assess the prevalence of and the factors associated with nasal carriage of <it>S. aureus </it>and its antibiotic sensitivity pattern among healthy children in Ujjain, India.</p> <p>Methods</p> <p>A prospective study was done in paediatric outpatient clinics of R.D. Gardi medical college Ujjain, India. Healthy children from 1 month to 59 months of age were included. Information on previously known risk factors for nasal colonization was collected using a pre-tested questionnaire. Swabs from anterior nares were collected and transported in Amies transport media with charcoal and cultured on 5% sheep blood agar. Antibiotic sensitivity tests were performed using Kirby Bauer's disc diffusion method according to performance standards of Clinical and Laboratory Standard Institute guidelines.</p> <p>Results</p> <p>Of the 1,562 children from 1-month up-to five years of age included in the study 98 children tested positive for nasal carriage of <it>S. aureus</it>. The prevalence of nasal carriage of <it>S. aureus </it>was 6.3% (95% CI 5.1-7.5) out of which 16.3% (95% CI 8.9-23.8) were methicillin-resistant <it>S. aureus </it>(MRSA). The factors associated with nasal carriage were "child attending preschool" (OR 4.26, 95% CI 2.25-8.03; <it>P </it>= 0.007) or "school" (OR 3.02, 95% CI 1.27-7.18; <it>P </it>< 0.001) and "family size more than 10 members" (OR 2.76 95% CI 1.06-7.15; <it>P </it>= 0.03). The sensitivity pattern of isolated <it>S. aureus </it>showed resistance to commonly used oral antibiotics while resistance to glycopeptides was not noted.</p> <p>Conclusions</p> <p>We found a relatively low rate of nasal carriage of <it>S. aureus </it>in children below five years when compared to children of older age groups in India. Yet, prevalence of MRSA was relatively high.</p

Recurrence of Primary Sclerosing Cholangitis After Liver Transplant in Children : An International Observational Study

Background and Aims Recurrent primary sclerosing cholangitis (rPSC) following liver transplant (LT) has a negative impact on graft and patient survival; little is known about risk factors for rPSC or disease course in children. Approach and Results We retrospectively evaluated risk factors for rPSC in 140 children from the Pediatric PSC Consortium, a multicenter international registry. Recipients underwent LT for PSC and had >90 days of follow-up. The primary outcome, rPSC, was defined using Graziadei criteria. Median follow-up after LT was 3 years (interquartile range 1.1-6.1). rPSC occurred in 36 children, representing 10% and 27% of the subjects at 2 years and 5 years following LT, respectively. Subjects with rPSC were younger at LT (12.9 vs. 16.2 years), had faster progression from PSC diagnosis to LT (2.5 vs. 4.1 years), and had higher alanine aminotransferase (112 vs. 66 IU/L) at LT (all P < 0.01). Inflammatory bowel disease was more prevalent in the rPSC group (86% vs. 66%; P = 0.025). After LT, rPSC subjects had more episodes of biopsy-proved acute rejection (mean 3 vs. 1; P < 0.001), and higher prevalence of steroid-refractory rejection (41% vs. 20%; P = 0.04). In those with rPSC, 43% developed complications of portal hypertension, were relisted for LT, or died within 2 years of the diagnosis. Mortality was higher in the rPSC group (11.1% vs. 2.9%; P = 0.05). Conclusions The incidence of rPSC in this cohort was higher than previously reported, and was associated with increased morbidity and mortality. Patients with rPSC appeared to have a more aggressive, immune-reactive phenotype. These findings underscore the need to understand the immune mechanisms of rPSC, to lay the foundation for developing new therapies and improve outcomes in this challenging population.Peer reviewe

Assessing the Validity of Adult-derived Prognostic Models for Primary Sclerosing Cholangitis Outcomes in Children

Background: Natural history models for primary sclerosing cholangitis (PSC) are derived from adult patient data, but have never been validated in children. It is unclear how accurate such models are for children with PSC. Methods: We utilized the pediatric PSC consortium database to assess the Revised Mayo Clinic, Amsterdam-Oxford, and Boberg models. We calculated the risk stratum and predicted survival for each patient within each model using patient data at PSC diagnosis, and compared it with observed survival. We evaluated model fit using the c-statistic. Results: Model fit was good at 1 year (c-statistics 0.93, 0.87, 0.82) and fair at 10 years (0.78, 0.75, 0.69) in the Mayo, Boberg, and Amsterdam-Oxford models, respectively. The Mayo model correctly classified most children as low risk, whereas the Amsterdam-Oxford model incorrectly classified most as high risk. All of the models underestimated survival of patients classified as high risk. Albumin, bilirubin, AST, and platelets were most associated with outcomes. Autoimmune hepatitis was more prevalent in higher risk groups, and over-weighting of AST in these patients accounted for the observed versus predicted survival discrepancy. Conclusions: All 3 models offered good short-term discrimination of outcomes but only fair long-term discrimination. None of the models account for the high prevalence of features of autoimmune hepatitis overlap in children and the associated elevated aminotransferases. A pediatric-specific model is needed. AST, bilirubin, albumin, and platelets will be important predictors, but must be weighted to account for the unique features of PSC in children.Peer reviewe

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Identifying Key Benefits in European Off-Patent Biologics and Biosimilar Markets: It is Not Only About Price!

Biosimilar medicines have shown similarity with the originator biologic and offer a similar clinical outcome generally at a lower cost. This paper identifies benefits of off-patent biologics and biosimilars, and illustrates these benefits with empirical data from Europe. We provide a narrative review of published literature on values and benefits of biosimilars in Europe. The results describe cost savings as the key driver stemming from the lower price of biosimilars, than that of originator products, and from price competition between biosimilar(s), originator, and next-generation products. Cost savings may then translate into a number of other associated benefits. The lower price of biosimilars and similar effectiveness to the originator biologics improve cost effectiveness, implying that reimbursement can be granted or extended to other patient groups, or that the biologic therapy can be moved to an earlier line of treatment. Cost savings from biosimilars can be used to increase patient access to therapy or to increase the number of healthcare professionals. Finally, competition between off-patent biologics and biosimilars may stimulate an innovation in the formulation and development of next-generation biologics. Our paper illustrates that the benefit of off-patent biologics and biosimilars is not restricted to cost savings, but that these medicines may contribute to an expansion of medical treatment options for patients, hence concomitantly contributing to the long-term sustainability of the healthcare system. This review provides a broader view for clinical and economic decision makers and healthcare professionals on the added benefits of off-patent biologics and their use in clinical practice.status: publishe

Identifying Key Benefits in European Off-Patent Biologics and Biosimilar Markets: It is Not Only About Price!

Biosimilar medicines have shown similarity with the originator biologic and offer a similar clinical outcome generally at a lower cost. This paper identifies benefits of off-patent biologics and biosimilars, and illustrates these benefits with empirical data from Europe. We provide a narrative review of published literature on values and benefits of biosimilars in Europe. The results describe cost savings as the key driver stemming from the lower price of biosimilars, than that of originator products, and from price competition between biosimilar(s), originator, and next-generation products. Cost savings may then translate into a number of other associated benefits. The lower price of biosimilars and similar effectiveness to the originator biologics improve cost effectiveness, implying that reimbursement can be granted or extended to other patient groups, or that the biologic therapy can be moved to an earlier line of treatment. Cost savings from biosimilars can be used to increase patient access to therapy or to increase the number of healthcare professionals. Finally, competition between off-patent biologics and biosimilars may stimulate an innovation in the formulation and development of next-generation biologics. Our paper illustrates that the benefit of off-patent biologics and biosimilars is not restricted to cost savings, but that these medicines may contribute to an expansion of medical treatment options for patients, hence concomitantly contributing to the long-term sustainability of the healthcare system. This review provides a broader view for clinical and economic decision makers and healthcare professionals on the added benefits of off-patent biologics and their use in clinical practice

Bimatoprost versus clobetasol propionate in scalp alopecia areata: A prospective non-randomized open-label clinical trial

Background: Alopecia areata (AA) is one of the most common forms of alopecia presenting to the dermatology out patient department (OPD) worldwide as well as in Nepal. It is mostly diagnosed clinically. Treatment depends on the extent, location, and severity of the condition. Various treatment options available are topical, intralesional, and oral medications. Bimatoprost is a relatively newer treatment modality in AA. Aim and Objective: To compare the efficacy and safety of topical bimatoprost 0.01% solution versus clobetasol propionate 0.05% cream in scalp AA. Materials and Methods: A total of 50 patients attending the dermatology OPD of a tertiary hospital between March 2018 and February 2019 were included in this prospective non-randomized open-label clinical trial. Patients were divided into two groups i.e., Group A- topical bimatoprost solution 0.01% and Group B- topical clobetasol propionate cream 0.05%, and followed up at weeks 4, 8, and 12. The improvement was analyzed subjectively by hair regrowth and objectively by Severity of Alopecia Tool (SALT) score. Side effects, nature of terminal hair and onset of initial response were also recorded. Results: Out of 50 patients, 27 were males and 23 were females with a mean age of 28.5 ± 9.34 years and mean duration of disease of 18.67 ± 46.1 weeks. Hair regrowth rate and reduction in SALT score from baseline were seen more in clobetasol group compared to bimatoprost (p = 0.282 and P = 0.246, respectively). Side effects were seen more in the clobetasol group compared to bimatoprost group (p = 0.002). Onset of cosmetically acceptable hair regrowth was seen earlier in the bimatoprost group (p = 0.017) and also the nature of regrown hairs was more pigmented in bimatoprost group (p = 0.024). Conclusions: There is no significant difference in hair regrowth between clobetasol and bimatoprost in the treatment of AA on scalp at the end of 12 weeks, although bimatoprost has an advantage of lesser side effects, more rapid response and growth of more pigmented hairs

Decision making in the treatment of peripheral arterial disease - A single-institution comparative study using information from color doppler and digital subtraction angiogram studies

Background: Numerous studies have compared the accuracy of color Doppler (CD) with that of digital subtraction angiography (DSA) in the diagnosis of peripheral arterial disease (PAD). However, only a few have looked at the influence of these diagnostic tests on the treatment decision in PAD. Aim: This study evaluated the differences in treatment decisions that were based on CD and with those based on DSA findings. Methods and Materials: Findings from CD and DSA studies obtained in 40 patients were entered on line diagrams by two radiologists working separately. These were randomized and sent to three experienced clinicians - two vascular surgeons and one interventional radiologist. The treatment decisions of the clinicians based on each proforma were collected and analyzed to look for the degree of agreement between Doppler-based and DSA-based decisions. Results: There was fair to moderate agreement between CD-based and DSA-based decisions for all three clinicians, with some improvement in agreement with the addition of clinical data. The vascular surgeons showed better agreement with each other on treatment decisions compared to the interventional radiologist who showed a fair-to-moderate level of agreement with the vascular surgeons, which did not significantly change with the addition of clinical data. Conclusion: There is a fair to moderate agreement between treatment decisions based on CD findings and those based on DSA findings. We conclude that CD along with clinical data is sufficient to make decisions in the treatment of PAD

Fabrication of the Mesoporous Fe@MnO₂NPs–MCM-41 Nanocomposite: An Efficient Photocatalyst for Rapid Degradation of Phenolic Compounds

Incorporation of nanoparticles in the extraframework of MCM-41 and its effect on the photocatalytic degradation of phenol has been studied. Mesoporous MnO₂ nanoparticles (meso-MnO₂NPs) are incorporated <i>in situ</i> into the extraframework of MCM-41 during its synthesis to obtain mesoporous MnO₂NPs–MCM-41­(MM) materials. Three samples of mesoporous MnO₂NPs–MCM-41 have been prepared with Si/Mn ratios 10, 50, and 90. The sample with Si/Mn ratio 10 shows better textural properties compared to the other two samples. Formation of meso-MnO₂NPs, reversible coordination of Mn ⇄ Si, and formation the Fe-modified MM-10 nanocomposite (mesoporous Fe@MM–10 NC) are the crucial steps involved in the present investigation. The role of CTAB, NH₃, and (NH₄)₂S₂O₈ are the key ingredients for the fabrication of meso-MnO₂NPs and mesoporous Fe@MM–10 NC. The materials are characterized by LXRD, N₂ sorption, and HRTEM to evaluate the mesoporosity, morphology, and textural properties. Mesoporous Fe@MM–10 NC was treated as an efficient photocatalyst for degradation of phenolic compounds, an exemplary move. Nearly 100% degradation of concentrated phenolic compounds (100 mg L^–1) has been achieved within 45 min by mesoporous 5Fe@MM–10 NC. Intraparticle mesoporosity, small particle sizes of the nanocomposite, the formation of a large number of ^•OH radicals, and the generation of high photocurrent are important factors for swift degradation of phenolic compounds by mesoporous 5Fe@MM–10 NC material