Approval Criteria Research Articles

Statement concerning the review of the approval of the active substance pirimicarb.

On 26 August 2022, the European Commission asked EFSA to provide scientific and technical assistance according to Article 21(2) of Regulation (EC) No 1107/2009 concerning the review of the approval of the active substance pirimicarb and to deliver a statement on whether the applicable approval criteria may still be considered fulfilled, taking into consideration the information submitted by the applicant and the assessment of the rapporteur Member State, Sweden and, where applicable, the results of a discussion with experts from Member States. The current statement contains a summary of the main findings of the assessment of the risks to consumers from the exposure to metabolites of pirimicarb through dietary intake, the risks to human health through non-dietary exposure and the acute risk to birds from the representative uses of pirimicarb assessed for the first approval and additionally, from the representative uses as submitted as part of the renewal of approval. Concerns are reported where identified.

A Critical Analysis of Completed Abandoned Construction Projects in Ghana

The paper presents findings from a study of abandoned infrastructure projects and provides recommendations to lessen the adverse effects of infrastructural sustainability in Ghana. The study adopted a mixed-method approach, using face-to-face interviews, and a questionnaire survey. Responses were received from selected government officials, consultants, and end-users involved in selecting and approving government projects in the Metropolitan, Municipal, and District Assemblies (M.M.D.A.s) of the 16 regions of Ghana. Qualitative data gathered from an interview of 45 candidates were transcribed and coded with Atlas ti eight and line-by-line content analysis. Whilst, quantitative data from questionnaires completed by 320 respondents were analysed by the researcher with the aid of Mann- Whitney U-test in Statistical Package for Social Sciences (S.P.S.S.) to evaluate the magnitude of the impacts of completed project abandonment in Ghana. Findings indicate that completed project abandonment exists in Ghana, and its economic, social, and environmental implications are considerable on the long-term sustainability of infrastructure development and the country's overall economic growth. Infrastructural sustainability was found to be equally contingent on the initial stages of project preparation. The study draws readers’ attention to the critical role of project selection and approval criteria. The study identified critical impacts of project selection and approval process and the construction industry's long-term sustainability.

Perancangan Modul Persetujuan Otomatis dan Klasifikasi pada Sistem Persetujuan Lapor Diri Pensiun Menggunakan FSA

Retired Dana Pensiun Perkebunan Defined Benefit Pension Plan (PPMP) participants are required to certify annually that they still meet the criteria for being a valid pensioner. The retiree uses the Dapenbun online application to take a photo of himself and her ID card and wait for the data to be processed by the administrator. Pensioners who do not report will have their pension entitlements suspended. The number of retirees managed by the Plantation Pension Fund is over 216,000, and managers are overwhelmed with approval at the start of the re-data period. For this reason, authors design systems that can run automated approval and classification systems to facilitate data approval. Applying the FSA concept to this system reduces the processing of participant data as automation is applied to the first process of automatic termination of pensions for children aged 21 and over, second data with criteria for automatic approval. It will be faster. Categorizing data reduces approval errors and makes it easier for users to approve data.

Advanced Technologies for Potency Assay Measurement.

Crucial for their application, cell products need to be well-characterized in the cell manufacturing facilities and conform to regulatory approval criteria before infusion into the patients. Mesenchymal Stromal Cells (MSCs) are the leading cell therapy candidate in clinical trials worldwide. Early phase clinical trials have demonstrated that MSCs display an excellent safety profile and are well tolerated. However, MSCs have also exhibited contradictory efficacy in later-phase clinical trials with reasons for this discrepancy including poorly understood mechanism of MSC therapeutic action. With likelihood that a number of attributes are involved in MSC derived clinical benefit, an assay that measures a single quality of may not adequately reflect potency, thus a combination of bioassays and analytical methods, collectively called "assay matrix" are favoured for defining the potency of MSC more adequately. This chapter highlights advanced technologies and targets that can achieve quantitative measurement for a range of MSC attributes, including immunological, genomic, secretome, phosphorylation, morphological, biomaterial, angiogenic and metabolic assays.

ПРОВЕДЕННЯ МИРОТВОРЧИХ ОПЕРАЦІЙ: ВИКЛИКИ СУЧАСНОЇ МИРОТВОРЧОЇ ДІЯЛЬНОСТІ

The article examines approval criteria, stages of implementation, and problems associated with conducting peacekeeping operations. The study provides a comprehensive overview of the United Nations criteria for approving peacekeeping operations, including the need for the consent of the parties involved and the availability of resources. The article also outlines various stages of implementation. In addition, the paper highlights the challenges and issues often encountered in peacekeeping operations, such as lack of funding, insufficient resources and political complexities. Peacekeeping operations are becoming increasingly important in resolving conflicts and promoting peace around the world. However, conducting these operations is a complex process that requires careful planning and management. To meet these challenges, policymakers and practitioners must adopt a proactive approach to peacekeeping operations, including providing adequate funding and resources, promoting effective communication and cooperation, and prioritizing the safety and security of personnel involved. The article also highlights some of the key challenges facing peacekeeping operations in the modern era, including the changing nature of conflicts, the politicization of peacekeeping and the challenges of ensuring the safety of peacekeepers on the ground. In addition, the problems of resource allocation and coordination between various participants in peacekeeping activities, such as the UN, regional organizations and member states, are explored, calling for more attention to these challenges and more effective cooperation between all participants in peacekeeping operations. It emphasizes the need for a more nuanced and adaptive approach to peacekeeping that takes into account the unique circumstances of each conflict and utilizes the experience of all parties involved. Overall, the article highlights the importance of continuing efforts to improve the effectiveness and impact of peacekeeping operations in the modern era.

Application of Realtime RT-PCR assay for the detection of E gene of SARS-CoV-2

Application on the Realtime RT-PCR assay is a method to determine the presence of viruses through the detection of genetic material of the SARS-CoV-2 virus, which is a highly accurate method. This study was conducted to validate the Realtime RT-PCR assay for the detection of E gene of SARS-CoV-2 at National Institute for Control of Vaccines and Biologicals (NICVB).
 Descriptive study in the laboratory. We determined limit of detection (LOD), reproducibility and analytical specificity of the Realtime RT-PCR assay for the detection of E gene of SARS-CoV-2 according WHO guidelines.
 The study results included as follow the limit of detection (LOD) reached LOD 95 is 5.2 copies/reaction (95%CI 3.3- 8.0); The accuracy with mean CV (%) of repeatability reached 2.00% and reproducibility reached 1.74% and analytical specificity reached 100%. The results all met the approval criteria and comparable to published data by WHO group.
 Based on results we successful application of Realtime RT-PCR assay for the detection of E gene of SARS-CoV-2 at National Institute for Control of Vaccines and Biologicals

Recommendations for laboratory testing of UK patients with acute myeloid leukaemia.

Recommendations for laboratory testing of UK patients with acute myeloid leukaemia.

Battered by Geopolitical Winds, Bulgaria Struggles to Restart Much Needed Reforms

Battered by Geopolitical Winds, Bulgaria Struggles to Restart Much Needed Reforms

Functional requirements of a mobile-based application for stroke self-management: A Delphi study.

This study aimed to determine the functional requirements of a self‐management mobile application for stroke survivors. For extracting the initial functional requirements, a literature review as well as interviews with 17 patients and caregivers were done. The results were analyzed using the content analysis method. The initial extracted requirements were then provided to the specialists by the Delphi technique to determine the final functional requirements. Content validity ratio (CVR) and content validity index (CVI) were calculated according to the Lawshe model. Criteria for item approval included CVR > 0.49 and CVI > 0.79. Finally, the approved items were turned into a five‐point Likert scale questionnaire and were then provided to 53 experts and items with a mean score higher than 3.75 were approved. Functional requirements including creating a user account, educational material, support services, providing reminders and alerts for drugs administration and physician appointments, and rehabilitation exercises (to improve balance, upper and lower extremities rehabilitation, and activities of daily living (ADLs)) were approved. Most of the approved functional requirements were related to rehabilitation exercises for improving upper limb motor function. The experts did not approve the requirements for using splints and slings or the recommendation to take some medications.

P782: IMMUNOPHENOTYPIC AND MOLECULAR GENETIC MARKERS OF UNFAVORABLE PROGNOSIS IN PATIENTS WITH MYELODYSPLASTIC SYNDROME

Background: Therapy is selected based on risk, need for transfusion of blood components, percentage of bone marrow blasts, and cytogenetic profile. In low-risk groups, the goal of treatment is to reduce the need for replacement therapy and prevent transformation to higher-risk or AML. In higher risk groups, the goal is to prolong survival. Currently, there are no approved criteria for selecting therapy for patients with MDS based on the classifications and prognostic scales used, treatment regimens for progression of MDS or its refractory forms. Aims: The aim of the study was to identify unfavorable prognostic immunophenotic and molecular genetic markers of blast cells in patients with high-risk myelodysplastic syndrome Methods: The prospective cohort study included 68 patients with newly diagnosed MDS in the period from January 2017 to December 2021. The patients underwent a primary diagnostic complex of MDS, including immunophenotyping and molecular genetic research of bone marrow aspirate. The age of patients is 25-82 years, the median age is 64 years. According to the IPSS classification included: high risk (10 pats), intermediate-2 (26 pats), intermediate-1 (26 pats), low risk (6 pats). According to the IPSS-R classification included: very high risk (23 pats), high risk (17 pats), intermediate (14 pats), low risk (12 pats), very low risk (2 pats). The following molecular genetic markers were found: complex aberrations >3 (10 pats), trisomy 8 chromosome (8 pats), absence of molecular genetic disorders (27 pats), isolated 5q chromosome (13 pats), any changes of the 7 chromosome (8 pats), deletion of the 20 chromosome (3 pats), deletion of the 11 chromosome (1 pats), TP53 (2 pats). To explore immunophenotic and molecular genetic markers we use three state “illness-death” model. We consider the following states: diagnosis, transformation into leukemia; death. Results: We identified high-risk immunophenotypic and molecular genetic markers - · for transition “diagnosis-death”: - CD38 <50% HR 3.7 (1.2-11.5 CI; p = 0.022), - CD13> 50% HR 8.7 (1.1-67.8 CI; p = 0.04), - complex aberrations >3 HR 5.8 (1.4-24.6 CI; p=0,015); - · for transition “diagnosis-transformation”: - CD71 ≥65% HR 4.1 (1.35-12.4 CI; p = 0.013); - CD13> 75% HR 2.8 (1.1-7.1 CI; p = 0.034), - complex aberrations >3 HR 2.8 (0,86-9,0 CI; p=0,087); - · for transition “transformation-death“: - CD25 <5% HR 6.3 (1.4-28 / 4 CI; p = 0.017), - CD 33 <50% HR 6.6 (1.3-34.7 CI; p = 0.026)), - complex aberrations >3 HR 0,22 (0,06-0,84 CI; p=0,027), - trisomy 8 chromosome HR 7.9 (0.71-88 CI; р=0,093). Figure 1 – The probability of various conditions depending on the time since the diagnosis. State 1 - estimation of the probability of being in the state «diagnosis-transformation» State 2 - estimation of the probability of being in the state «transformation-death» State 3 - estimation of the probability of being in the state «diagnosis-death» Image:Summary/Conclusion: The selection of groups of patients with identified immunophenotypic and molecular genetic markers of a high risk of transformation into acute leukemia and a high risk of death (“diagnosis-death”: CD38<50%, CD13>50%, complex aberrations>3; “diagnosis-transformation”: CD71≥65%, CD13>75%, complex aberrations>3; “transformation-death“: CD25<5%, CD33<50%, complex aberrations>3, trisomy 8 chromosomes) requires consideration of a new approach to therapy.

Poor Antifungal Coverage for Onychomycosis in a Cross-Sectional Analysis of Medicaid Formularies.

Onychomycosis is the most common nail disease seen in clinical practice. Medication safety, severity of disease, comorbidities, concomitant medications, patient age, and cost are all important considerations when treating onychomycosis. Because cost may affect treatment decisions, we sought to analyze Medicaid formulary coverage of onychomycosis antifungals. Public state Medicaid formularies were searched for coverage of US Food and Drug Administration-approved onychomycosis medications and off-label oral fluconazole. Total drug cost for a single great toenail was calculated using the National Average Drug Acquisition Cost. Pearson correlation coefficients were calculated to compare coverage and cost, mycologic cure rate, and complete cure rate. Oral terbinafine and off-label fluconazole were widely covered for onychomycosis treatment. There was poor coverage of oral itraconazole and topical ciclopirox, and there was no coverage of topical efinaconazole and tavaborole without step-edits or prior authorization. There was a significant negative correlation between medication coverage and cost (r = -0.758; P = .040). There was no correlation between medication coverage and mycologic (r = 0.548; P = .339) and complete (r = 0.768; P = .130) cure rates. There is poor Medicaid coverage of antifungals for the treatment of onychomycosis, with step-edits and prior authorization based on cost rather than treatment safety and efficacy. We recommend involving podiatrists and dermatologists in developing criteria for insurance approval of onychomycosis treatments.

Efficacy and Safety Considerations With Dose-Reduced Direct Oral Anticoagulants

ImportanceDose-reduced regimens of direct oral anticoagulants (DOACs) may be used for 2 main purposes: dose-adjusted treatment intended as full-intensity anticoagulation (eg, for stroke prevention in atrial fibrillation [AF] in patients requiring dose reduction) or low-intensity treatment (eg, extended-duration treatment of venous thromboembolism [VTE]). We reviewed randomized clinical trials (RCTs) to understand the scenarios in which dose-adjusted or low-intensity DOACs were tested and reviewed the labeled indications by regulatory authorities, using data from large registries to assess whether the use of dose-reduced DOACs in routine practice aligned with the findings of RCTs.ObservationsAmong 4191 screened publications, 35 RCTs that used dose-adjusted DOACs were identified for dabigatran, apixaban, rivaroxaban, and edoxaban. Of these 35 RCTs, 29 were related to stroke prevention in AF. Efficacy and safety results for dose-adjusted DOACs in large RCTs of AF were similar to those found for full-dose DOACs. To our knowledge, dabigatran, apixaban, and rivaroxaban have not been studied as dose-adjusted therapy for acute VTE treatment. Low-intensity DOACs were identified in 37 RCTs. Low-intensity DOACs may be used for extended-duration treatment of VTE (apixaban and rivaroxaban), primary prevention in orthopedic surgeries (dabigatran, apixaban, and rivaroxaban), primary prevention in ambulatory high-risk cancer patients (apixaban and rivaroxaban) or (postdischarge) high-risk medical patients (rivaroxaban), in stable atherosclerotic vascular disease, or after a recent revascularization for peripheral artery disease in conjunction with aspirin (rivaroxaban). Minor variations exist between regulatory authorities in different regions regarding criteria for dose adjustment of DOACs. Data from large registries indicated that dose-reduced DOACs were used occasionally with doses or for clinical scenarios different from those studied in RCTs or recommended by regulatory authorities.Conclusions and RelevanceDose adjustment and low-intensity treatment are 2 different forms of dose-reduced DOACs. Dose adjustment is mostly relevant for AF and should be done based on the approved criteria. Dose adjustment of DOACs should not be used for acute VTE treatment in most cases. In contrast, low-intensity DOACs may be used for primary or secondary VTE prevention for studied and approved indications. Attention should be given to routine practice patterns to align the daily clinical practice with existing evidence of safety and efficacy.

Development and implementation of a national online application system for cross-jurisdictional linked data

The Population Health Research Network (PHRN) is an Australian national data linkage infrastructure that links a wide range of health and human services data in privacy-preserving ways. The data linkage infrastructure enables researchers to apply for access to routinely collected, linked, administrative data from the six states and two territories which make up the Commonwealth of Australia, as well as data collected by the Australian Government. The PHRN is a distributed network where data is collected and managed at the respective jurisdictional and/or cross-jurisdictional levels. As a result, access to linked data from multiple jurisdictions requires complex approval processes. This paper describes Australia’s approach to enabling access to linked data from multiple jurisdictions. It covers the identification of, and agreement to, a minimum set of data items to be included in a unified national application form, the development and implementation of a national online application system and the harmonisation of business processes for cross-jurisdictional research projects. Utilisation of the online application system and the ongoing challenges of data linkage across jurisdictions are discussed. Changes to the data custodian and ethics committee approval criteria were out of scope for this project.

An independent reader system that parallels critical steps of full automation capability for immunohematology testing

IntroductionUse of fully automated solutions to perform analysis of immunohematology tests is highly desirable as it delivers an improved level of safety and security of results. However, full automation may not be feasible financially and practically in all circumstances. A solution that addresses most of the process step hazards of manual testing can assist in achieving a higher level of confidence in and safety of test results. MethodsThe study utilized a column agglutination technology (ORTHO BioVue ® System) to test a variety of samples on the ORTHO VISION ® Analyzer and compare to the reader capability of the ORTHO OPTIX™ Reader. Both direct agglutination and direct/indirect antiglobulin test methods were evaluated. The data was analysed for per cent agreement and for concordance at the lower bound 95% confidence interval. The acceptance criteria for concordance for direct agglutination was ≥ 99.4% and for indirect agglutination was ≥ 98.0% at a lower bound 95% confidence interval. ResultsThere were 13,805 columns producing 5174 interpreted tests for direct agglutination and 5998 columns producing 2958 interpreted direct/indirect antiglobulin tests evaluated. Testing demonstrated that direct agglutination and direct/indirect antiglobulin testing generated greater than 99% concordance between the fully automated instrument system and the reader. ConclusionsThe reader exceeded the approval criteria set for the study which demonstrates the capability to address the desire for a solution that moves manual testing to an enhanced level which achieves improved safety and security in immunohematology testing.

Does Medicaid Cover Penile Prosthesis Surgery? A State-by-State Analysis

ABSTRACT Introduction Malleable [MPP] and inflatable [IPP] penile prosthesis surgery for the management of erectile dysfunction is a reliable treatment option with high success rates and excellent patient satisfaction; however, Medicaid coverage transparency is poor leaving a knowledge gap in this population. Objective The present study seeks to assess Medicaid coverage for MPP and IPP by state as evidenced by inclusion in publicly available physician fee schedules. Methods State Medicaid websites were utilized to access public physician fee schedules. Individual search queries were performed for CPT codes 54400 and 54405 which represent insertion of MPP and IPP, respectively. Data were recorded for each device including the coverage status, physician fees, and the presence of clear documentation of a prior authorization requirement. Results Medicaid physician fee schedules were accessible for 49 out of 50 US states, and 28 states reported coverage for at least one type of penile prosthesis (Figure). Two states reported coverage for MPP only, one state reported coverage for IPP only, and 24 states reported coverage for both devices. One state reported that it did not cover either device, but listed coverage for a self-contained IPP (CPT 54401) only. Mean physician reimbursement was $477.15 (290.82–$1175.50) for MPP placement and $691.76 (421.68–$1794.27) for IPP (Table 1). Eleven states documented prior authorization requirements within their fee schedules, while the remaining 17 states did not. Criteria for approval for prior authorization were not clearly stated in any fee schedule. Conclusions Efforts to clearly document approval criteria and educate Men's Health providers on available coverage could result in a significant improvement in sexual satisfaction in the Medicaid population. Graphical representation of states offering Medicaid penile prosthetic coverage and physician reimbursement ranges are provided with comparison to Medicare rates (Figure). Limitations include heterogeneity in fee schedules, lack of prior authorization requirement details, inability to correlate to successful claims data, and the evolving nature of Medicaid coverage for the given procedures. Medicaid coverage exists for penile prosthetic surgery in 28 states, although often with significant non-transparent prior authorization criteria. Disclosure No

Quality of biomarker defined subgroups in FDA approvals of PD-1/PD-L1 inhibitors 2014 to 2020.

PD-L1 expression is associated with differential response in cancers treated with checkpoint inhibitors. Clinical trials for Food and Drug Administration (FDA) approvals of programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors include limited subgroup analyses based on PD-L1 expression. We aimed to define the characteristics of PD-L1 defined subgroups of clinical trials leading to FDA approvals for new indications of PD-1/PD-L1 inhibitors. FDA approvals for PD-1/PD-L1 inhibitors from January 2014 to December 2020 were identified and the clinical trials leading to each drug approval were reviewed. We collected key variables from publicly available information on FDA website and peer-reviewed publications of clinical trials. We assessed regulatory characteristics (approval date, approved drug[s], cancer type, line of therapy and biomarker-restricted approval criteria) of each approval. Clinical trials leading to approvals were reviewed for trial design (RCT vs single arm study, primary endpoint) and PD-L1 defined subgroup design (no subgroup analysis, single threshold 2-group analysis, nested subgroups and adjacent subgroups). We then compared regulatory and trials characteristics (trial design, primary endpoint and biomarker approval criteria) between studies with nested and adjacent subgroups. There were 60 approvals for PD-1/PD-L1 inhibitors between January 2014 and December 2020. Twelve of 60 (20%) did not include any PD-L1 subgroups. Twenty-five of 60 (42%) approvals reported only two subgroups, 14 (23%) included adjacent subgroups and 9 (15%) had nested subgroups. Twenty-five of 60 trials (42%) are single arm studies. Comparison of characteristics between trials with nested subgroup design and adjacent subgroup design did not show differences. We conclude that approvals for new indications of PD-1/PD-L1 inhibitors are based on studies that do not include comprehensive reporting of outcomes by PD-L1 biomarker subgroups.

BIOCHEMICAL AND CLINICAL CHARACTERIZATION OF IODINE DEFICIENCY DISORDERS IN CENTRAL INDIA

Background: Iodine (I) is a trace element that is required by both humans and animals. It can be found in a variety of chemical forms, including iodine, iodide (I), and iodate (IO3). It is widely distributed across the earth's ecology, with a concentration in the oceans. Iodine entered the natural cycle from the ocean, the atmosphere, and rainfall, as well as from rainfall into streams and rivers. Iodine is absorbed as iodide in human nutrition. Iodine is a necessary micronutrient and a component of thyroid hormones. Fish and seafood have a high iodine level. The amount of iodine in soil and drinking water varies depending on where it comes from. Iodine shortage produces a variety of negative health consequences, which are referred to as iodine deficiency illnesses (IDD). These conditions are caused by a lack of iodine, which causes insufficient thyroid hormone production.&#x0D; Aim: The aim of this study is to characterize the iodine deficiency disorder by biochemical and clinical assessment and to correlate the iodine status with thyroid disorder(s) in adults.&#x0D; Material and Method: The samples for this investigation were taken from patients at the Department of Endocrine Surgery. This study comprised a total of 100 hundred goiter patients, who had their urinary iodine excretion and thyroid hormone levels examined. For all goiter patients, the grading of goitre was established using the WHO/UNICEF/ICCIDD approved criteria. TSH, Free T4, Free T3 by using ELISA Method using commercial kits. Anti-microsomal antibody (AMA) or Thyroperoxidase antibody (TPO-Ab) by using ELISA Method using commercial kits. Anti-thyroglobulin antibody (ATG) estimated by using ELISA Method using commercial kits.&#x0D; Results: The data for each group were presented as Median and inter quarter range (IQR) The median and IQR of Urinary iodine excretion of the hypothyroid, hyperthyroid and Euthyroid goiter subjects were respectively and there was significant difference in the median urinary iodine excretion. The median and IQR of Urinary iodine excretion of the thyroiditis, thyrotoxicosis, cancer of thyroid and benign goiter respectively and there was significant difference in the median urinary iodine excretion.&#x0D; Conclusion: For ages, endemic goitre and cretinism have been recognised as public health issues, and iodine deficiency is thought to be the leading cause of preventable mental retardation. Most countries now include iodine deficiency control as part of their national nutrition policies. To eliminate iodine deficiency, several therapies with high efficacy have been employed, including iodized oil capsules (IOC) and universal salt iodisation (USI). Although some progress has been made, efforts to eliminate this devastating health problem must be hastened. Not only should iodine deficiency be monitored, but so should excessive iodine intake, as this is a problem in various areas, including the camps.&#x0D; Keywords: IDD, Goitre, TSH, IOC, USI, ATG, AMA, T4, T3.

Clinical and Financial Impact of a Diagnostic Stewardship Program for Children with Suspected Central Nervous System Infection

To investigate the optimal implementation and clinical and financial impacts of the FilmArray Meningitis Encephalitis Panel (MEP) multiplex polymerase chain reaction testing of cerebrospinal fluid (CSF) in children with suspected central nervous system infection. A pre-post quasiexperimental cohort study to investigate the impact of implementing MEP using a rapid CSF diagnostic stewardship program was conducted at Children's Hospital Colorado (CHCO). MEP was implemented with electronic medical record indication selection to guide testing to children meeting approved use criteria: infants <2months, immunocompromised, encephalitis, and ≥5 white blood cells/μL of CSF. Positive results were communicated with antimicrobial stewardship real-time decision support. All cases with CSF obtained by lumbar puncture sent to the CHCO microbiology laboratory meeting any of the 4 aforementioned criteria were included with preimplementation controls (2015-2016) compared with postimplementation cases (2017-2018). Primary outcome was time-to-optimal antimicrobials compared using log-rank test with Kaplan-Meier analysis. Time-to-optimal antimicrobials decreased from 28hours among 1124 preimplementation controls to 18hours (P<.0001) among 1127 postimplementation cases (72% with MEP testing conducted). Postimplementation, time-to-positive CSF results was faster (4.8 vs 9.6hours, P<.0001), intravenous antimicrobial duration was shorter (24 vs 36hours, P=.004), with infectious neurologic diagnoses more frequently identified (15% vs 10%, P=.03). There were no differences in time-to-effective antimicrobials, hospital admissions, antimicrobial starts, or length of stay. Costs of microbiologic testing increased, but total hospital costs were unchanged. Implementation of MEP with a rapid central nervous system diagnostic stewardship program improved antimicrobial use with faster results shortening empiric therapy. Routine MEP testing for high-yield indications enables antimicrobial optimization with unchanged overall costs.

Cellular and sub-chronic toxicity of hydroxyapatite porous beads loaded with antibiotic in rabbits, indented for chronic osteomyelitis

Bioceramics have emerged as a hopeful remedy for site-specific drug delivery in orthopaedic complications, especially in chronic osteomyelitis. The bioresorbable nature of bioceramic materials shaped them into a versatile class of local antibiotic delivery systems in the treatment of chronic osteomyelitis. Hydroxyapatite (HA) based bioceramics with natural bone mimicking chemical composition are of particular interest due to their excellent biocompatibility, better osteoconductive and osteointegrative properties. Although HA has been widely recognized as an efficient tool for local delivery of antibiotics, information regarding its subchronic systemic toxicity have not been explored yet. Moreover, a detailed investigation of in vivo subchronic systemic toxicity of HA is critical for understanding its biocompatibility and futuristic clinical applications of these materials as novel therapeutic system in its long haul. Evaluation of biocompatibility and sub-chronic systemic toxicity are significant determinants in ensuring biomedical device’s long-term functionality and success. Sub-chronic systemic toxicity allows assessing the potential adverse effects caused by leachable and nanosized wear particles from the device materials under permissible human exposure to the distant organs that are not in direct contact with the devices. In this context, the present study evaluates the sub-chronic systemic toxicity of in-house developed Hydroxyapatite porous beads (HAPB), gentamicin-loaded HAPB (HAPB + G) and vancomycin- loaded HAPB (HAPB + V) through 4 and 26-week muscle implantation in New Zealand white rabbits, as per ISO 10993–6 and ISO 10993–11. Analysis of cellular responses of HAPB towards Human Osteosarcoma (HOS) cell line through MTT assay, direct contact cytotoxicity, live/dead assay based on Imaging Flow Cytometry (IFC) showed its non-cytotoxic behaviour. Histopathological analysis of muscle tissue, organs like heart, lungs, liver, kidney, spleen, adrenals, intestine, testes, ovaries, and uterus did not reveal any abnormal biological responses. Our study concludes that the HAPB, gentamicin-loaded HAPB (HAPB + G) and vancomycin-loaded HAPB (HAPB + V) are biocompatible and did not induce sub-chronic systemic toxicity and hence satisfies the criteria for regulatory approval of HAs as a plausible candidate for clinical applications.

Treatment Options in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders.

There are few diseases where as much therapeutic progress has been made in recent years as in multiple sclerosis. Nine different drug classes with more than a dozen approved therapies are now available. Similarly, there have been unimaginable advances in understanding neuromyelitis optica (now neuromyelitis optica spectrum disorder [NMOSD]) over the past 15 years. Building on the knowledge gained, the first therapies have been approved in recent years. In this review, we aim to present all therapies approved for the treatment of MS or NMOSD. The different forms of application, different approval criteria and most important side effects will be presented. This work is intended for physicians who are interested in MS and NMOSD therapies and want to get a first overview and does not replace the respective guidelines of the regulatory authorities.