Consultant Members Research Articles

Influence of Public Participation on Implementation of County Government Projects: Case of Makueni County, Kenya

Projects are the foundation of local development in any nation that is developing. Despite the significance of county government projects to society, the majority of these initiatives have delayed, failed, or otherwise fallen short of their goals. The study aimed at assessing the influence of public participation on implementation of county government projects: case of Makueni County, Kenya. The study was guided by following specific objectives; to determine the influence of public participation in project identification process, budget preparation process, governance process and monitoring and evaluation process on implementation of Makueni county projects. A descriptive research design was used for this study. There were 330 project personnel working on projects throughout all Makueni County constituencies and this formed the study population. Thus, the target population was the project committee members, executive project management consultant members and technical officers involved in implementation of the projects for the last at least three years at Makueni sub-counties. Using a stratified random sampling procedure, 99 respondents (30% of the population) were chosen from the target population. The study used primary methods in data collection using questionnaires. Content analysis method was used to examine the qualitative data from the open-ended questions. The statistical package for social sciences (SPSS) version 22 was used to interpret the quantitative data from the closed-ended questions. Descriptive statistics, such as frequencies, percentages, standard deviation, and arithmetic mean, were used to examine the results. Inferential analysis was used in determination of the relationship between the variables. The results of the analysis were subsequently shown in charts and tables. The coefficient results show results that budget preparation process and governance process have a significant positive influence on project implementation, with standardized coefficients of 0.555 and 0.761, respectively. Meanwhile, monitoring and evaluation has a significant negative influence on project implementation with a standardized coefficient of -0.479. Project identification pross, on the other hand, does not have a statistically significant impact on project implementation.

The international impact of the National Institute for Health and Care Excellence and implications for the NHS

Market access consultant and editorial board member Steve Bojakowski discusses the impact of the National Institute for Health and Care Excellence and how this may change following new European Union regulations on health technology assessment.

Patients with Atopic Dermatitis Not on Systemic Therapy have High Rates of Severe, Uncontrolled Disease, and Considerable Impact on Quality of Life

Patients with Atopic Dermatitis Not on Systemic Therapy have High Rates of Severe, Uncontrolled Disease, and Considerable Impact on Quality of Life

Penerapan Metode Preference Selection Index (PSI) Dalam Pemilihan Anggota Badan Permusyawaratan Desa Kabupaten Bengkulu Selatan

Abstract :This thesis is the result of research that describes how much influence the Village Consultative Body has on the people of Tanjung Tebat Village, golden flower District, South Bengkulu Regency. The Village Consultative Body is an institution that embodies democracy in administering village governance. The Village Consultative Council can be considered as the village parliament. As for the background, the writer's interest in writing this thesis is based on the results of observations and initial interviews that the writer conducted at the golden flower sub-district office, where the selection of members of the Village Consultative Council still uses manual assessment or it can be said that it is not efficient. Where the author offers a Preference Selection Index method to be used in selecting the best Village Consultative Body.In the Preferences Selection Index method, the results are obtained by minimal and simple calculations as they are based on statistical concepts without the need for attribute weights. From the calculations, it can be concluded that the best village consultative body members in the golden flower District fall into alternative A5, namely Design Women with a total value of 0.9084 which has been resolved using the Prefence Selection Prefence Selection Index method.
 Keywords: Election of BPD Members, Method Prefence Selection Index

Orientasi Etika, Faktor Situasional dan Pengambilan Keputusan Etis dengan Komitmen Profesional Sebagai Pemoderasi

This study aims to empirically prove the effect of ethical orientation and situational factors on ethical decision making of tax consultants in Bali with professional commitment as a moderating variable. The research population of tax consultant members who are registered with the Indonesian Tax Consultants Association (IKPI) for the Bali Region is 278 people. The sampling technique used is saturated sampling technique with a total sample of 278 people. The research data was collected by distributing questionnaires and processed using the Partial Least Square (SEM-PLS) tool. The results of the analysis showed that ethical orientation of idealism, current information, moral intensity had a positive effect on ethical decision-making, while the ethical orientation of relativism, risk preference had a negative effect. on ethical decision making. In addition, professional commitment weakens the influence of ethical idealism orientation on ethical decision making, professional commitment strengthens the influence of relativism ethical orientation, and the current information on ethical decision making. Meanwhile, professional commitment cannot moderate the effect of risk preference and moral intensity on ethical decision making. The implications for tax consultants are to pay more attention to their ethical orientation and to pay attention to situational factors in order to create decisions that pay attention to ethics.
 Keywords: Ethical Decisions; Ethics; Situational Factors; Professional Commitment

Evaluation of Community Benefit Activities Among Nonprofit Hospitals, 2018-2021.

This study examined approaches that nonprofit hospitals use to evaluate community benefit activities in the Community Health Needs Assessment/Implementation Plan (CHNA/IP) process. Content analysis of CHNAs/IPs completed between 2018 and 2021 from a 20% stratified random sample (n = 503) of US nonprofit hospitals. A coding sheet was used to record details about the evaluation content reported by hospitals in their CHNAs/IPs. Evaluation was coded into 4 categories: (1) no mention of evaluation; (2) description of evaluation without reporting any measures; (3) reporting reach (number of people served) only; and (4) reporting social/health outcomes. For logistic regression analyses, categories 1 and 2 were grouped together into "no evaluation measures" and categories 3 and 4 were grouped into "evaluation measures" for binary comparison. Multinomial logistic regression was also used to individually examine categories 3 and 4 compared with no evaluation measures. While a majority of nonprofit hospitals (71.4%, n = 359) mentioned evaluation in their CHNAs, almost half (49.7%, n = 250) did not report any evaluation measures. Among the 50.3% (n = 253) of hospitals that reported evaluation measures, 67.2% (n = 170) only reported reach. Fewer than 1 in 5 hospitals (16.5%, n = 83) reported social/health outcomes. Hospitals that hired a consultant (adjusted odds ratio [AOR] = 1.61; 95% confidence interval [CI], 1.08-2.43) and system members (AOR = 1.76; 95% CI, 1.12-2.75) had higher odds of reporting evaluation measures. Using hospitals that reported no measures as the base category, system members (AOR = 7.71; 95% CI, 2.97-20.00) also had significantly higher odds of reporting social/health outcomes, while rural locations had lower odds (AOR = 0.43; 95% CI, 0.20-0.94). Although hospitals are required to evaluate the impact of actions taken to address the health needs identified in their CHNAs, few hospitals are reporting social/health outcomes of such activities. This represents a missed opportunity, as health/social outcomes could be used to inform the allocation of resources to maximize community benefits and the expansion of successful community initiatives.

Incentive mechanism for promoting the uptake of green building in South Africa

PurposeThe green building (GB) market is maturing after years of practice; therefore, incentives for promoting GB should be adapted to reflect the market transformation. Adapting incentives can positively influence stakeholders' motives, which in turn change stakeholders' behavioural intention towards GBs. Hence, this study aims to examine the parameters influencing the decision to adopt GB and to ascertain how incentive mechanisms promote the uptake of GB in South Africa.Design/methodology/approachUsing a scoping literature review and a sequential mixed research method, primary data were acquired from GB experts in four South African provinces. In analysing the quantitative data, the factors were ranked hierarchically using the mean ranking technique and factor analysis was computed to identify the underlying GB incentives. The qualitative data were analysed using content analysis.FindingsThe results indicate that incentive payment from a utility energy efficiency programme, rebates and discounts relating to environmentally friendly materials and products and providing grants to homeowners and developers to go towards certification were the most essential monetary incentives for promoting GB. In the category of non-monetary incentives, recognition of consultant team members and developers and free marketing/good publicity were the most important incentives. The incentive mechanisms were subsequently categorised as “Economic incentives” and “Reward scheme and technical support”.Research limitations/implicationsThis study was confined to four metropolitan areas in South Africa. Nevertheless, the outcomes have practical implications for GB projects in general and may serve as a good reference for other provinces in South Africa.Originality/valueThe findings of the study are a valuable resource for stakeholders such as the government, municipal assemblies, professional bodies and the Green Building Council of South Africa (GBCSA) in developing effective incentive mechanisms to promote GB adoption. This study adds to the body of knowledge relevant to GB incentivisation in South Africa.

LBA02-09 EMBARK: A Phase 3 Randomized Study of Enzalutamide or Placebo Plus Leuprolide Acetate and Enzalutamide Monotherapy in High-risk Biochemically Recurrent Prostate Cancer

LBA02-09 EMBARK: A Phase 3 Randomized Study of Enzalutamide or Placebo Plus Leuprolide Acetate and Enzalutamide Monotherapy in High-risk Biochemically Recurrent Prostate Cancer

Creating good village governance: an effort to prevent village corruption in Indonesia

PurposeThis study aims to investigate how the village government implements internal control, accountability, transparency and participation in the good governance practice for corruption prevention and detection in Indonesia.Design/methodology/approachThis study is qualitative research by conducting a semi-structured interview with village staff, village consultative council members and auditors.FindingsThe findings highlight three major issues contributing to poor governance and the failure to prevent and detect corruption.Practical implicationsThe regulator should urgently provide accounting standards, audit standards and internal control regulations for the village to create good governance for eradicating corruption.Originality/valueThis paper is a ground-breaking study that investigates the governance practice in the village as an anchor to solve the chronic corruption problem and offers a new direction of research in the village government.

Survey of liver pathologists to assess attitudes towards digital pathology and artificial intelligence

AimsA survey of members of the UK Liver Pathology Group (UKLPG) was conducted, comprising consultant histopathologists from across the UK who report liver specimens and participate in the UK National...

A Pilot Study of Heart Rate Variability Synchrony as a Marker of Intraoperative Surgical Teamwork and Its Correlation to the Length of Procedure.

Quality of intraoperative teamwork may have a direct impact on patient outcomes. Heart rate variability (HRV) synchrony may be useful for objective assessment of team cohesion and good teamwork. The primary aim of this study was to investigate the feasibility of using HRV synchrony in surgical teams. Secondary aims were to investigate the association of HRV synchrony with length of procedure (LOP), complications, number of intraoperative glitches and length of stay (LOS). We also investigated the correlation between HRV synchrony and team familiarity, pre- and intraoperative stress levels (STAI questionnaire), NOTECHS score and experience of team members. Ear, nose and throat (ENT) and vascular surgeons (consultant and registrar team members) were recruited into the study. Baseline demographics including level of team members' experience were gathered before each procedure. For each procedure, continuous electrocardiogram (ECG) recording was performed and questionnaires regarding pre- and intraoperative stress levels and non-technical skills (NOTECHS) scores were collected for each team member. An independent observer documented the time of each intraoperative glitch. Statistical analysis was conducted using stepwise multiple linear regression. Four HRV synchrony metrics which may be markers of efficient surgical collaboration were identified from the data: 1. number of HRV synchronies per hour of procedure, 2. number of HRV synchrony trends per hour of procedure, 3. length of HRV synchrony trends per hour of procedure, 4. area under the HRV synchrony trend curve per hour of procedure. LOP was inversely correlated with number of HRV synchrony trends per hour of procedure (p < 0.0001), area under HRV synchrony trend curve per hour of procedure (p = 0.001), length of HRV synchrony trends per hour of procedure (p = 0.002) and number of HRV synchronies per hour of procedure (p < 0.0001). LOP was positively correlated with: FS (p = 0.043; R = 0.358) and intraoperative STAI score of the whole team (p = 0.007; R = 0.493). HRV synchrony metrics within operating teams may be used as an objective marker to quantify surgical teamwork. We have shown that LOP is shorter when the intraoperative surgical teams' HRV is more synchronised.

Treatment persistence and adherence in people with type 2 diabetes switching to iGlarLixi vs free-dose combinations of basal insulin and glucagon-like peptide 1 receptor agonist.

BACKGROUND: Fixed-ratio combinations of basal insulin (BI) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have greater simplicity of administration with expected improved adherence/persistence with therapy, but real-world data are lacking. OBJECTIVE: To compare medication persistence, adherence, and health care resource utilization (HRU) and costs for insulin glargine 100 U/mL and the GLP-1 RA lixisenatide (iGlarLixi) with newly initiated free-dose combinations of BI and GLP-1 RAs initiated simultaneously or sequentially. METHODS: This analysis used the US Optum Clinformatics (January 2017 to November 2019) database and included data from adults (aged ≥ 18 years) with type 2 diabetes and a glycated hemoglobin A1c (A1c) of 8% or more. Participants received iGlarLixi or free-dose combinations of BI and GLP-1 RAs prescribed simultaneously or subsequently. Participants were followed for 12 months. Cohorts were propensity score matched on baseline characteristics. The primary outcome was persistence (days on treatment without discontinuation). Secondary outcomes were adherence (proportion of days covered), change in A1c, and all-cause and diabetes-related health care resource utilization and costs. Subgroup analyses were performed for individuals with A1c levels of 9% or more. RESULTS: After propensity score matching, there were 1,357 patients in each group; groups were well balanced. In the free-dose combination group, 65.6% started on BI, then added GLP-1 RAs; 28.5% started on GLP-1 RAs, then added BI; and 5.9% started on GLP-1 RAs and BI on the same day. In the subgroup with a baseline of A1c levels of 9% or more, 952 (iGlarLixi) and 932 (free-dose combination) participants were included. A significantly higher proportion of participants in the overall population who received iGlarLixi vs free-dose combinations were persistent (44.8% vs 36.3% [hazard ratio = 1.22, 95% CI = 1.11-1.35, P < 0.001]; the median [Q1, Q3] number of persistent days was 150 [63, 360] vs 120 [60, 310]) and adherent to therapy (41.3% vs 18.7%, [odds ratio = 3.06, 95% CI = 2.57-3.65; P < 0.001]). Results for persistence in the subpopulation of participants with HbA1c levels of 9% or more were similar. Reductions in A1c from baseline were similar between iGlarLixi and the free-dose combination group (overall population: -1.2% vs -1.3%; P = 0.1913), but the number of participants in the database with follow-up A1c data was low. All-cause and diabetes-related pharmacy visits and total medication and diabetes medication pharmacy claims costs were significantly lower (all P < 0.001) for those receiving iGlarLixi vs free-dose combinations in both populations. CONCLUSIONS: In adults with type 2 diabetes, iGlarLixi was associated with longer persistence by approximately 30 days, improved adherence, and reductions in outpatient and pharmacy visits and in pharmacy costs. DISCLOSURES: This study was funded by Sanofi US. Medical writing support was provided by Barrie Anthony, PhD, CMPP, of Evidence Scientific Solutions and funded by Sanofi US. Dr Edelman has been on an advisory board and speakers' bureau for AstraZeneca, MannKind, and Xeris and on an advisory board for BrightSight and is a board member for Senseonics and Team-Type1. Mr Cassarino is on the speakers' bureau for Sanofi. Dr Kayne has been a consultant and speakers' bureau member for AstraZeneca, Bayer, Dexcom, Eli Lilly & Company, Janssen, MannKind, Novo Nordisk, and Sanofi. Dr Dex and Mr Li are employees of Sanofi. Dr Pasquel has received unrestricted research support from Dexcom, Insulet, and Merck and has been a consultant for Medscape, AI Health, Boehringer Ingelheim, and Dexcom.

Foramen magnum decompression for Chiari malformation type I – UK surgical practice

Background: Symptomatic Chiari 1 malformation (CM1) is a common condition in Neurosurgery. Surgery involves hindbrain decompression and restoration of CSF flow through different surgical approaches. No Class 1 evidence exists to suggest the superiority of any of the surgical techniques. Aims: To investigate current surgical practice for symptomatic CM1 patients in the United Kingdom (UK) and determine the willingness to participate in a randomised controlled trial (RCT) comparing different surgical techniques. Methods: An electronic survey was sent to consultant members of the Society of British Neurological Surgeons and the British Chiari-Syringomyelia Group. The questions covered pre-operative and intra-operative management, presence of equipoise/uncertainty in optimal technique and willingness to participate in an RCT. Results: 98 responses were received. 67% operate on adults. 30% on adult and paediatric patients. There is variation in routine pre-operative use of: ICP monitoring (18%), flexion/extension x-rays (16%), venography (20%) and ophthalmology assessment (26%). 18% of neurosurgeons would not offer foramen magnum decompression when the presenting symptom is only refractory cough/sneeze headache. 15% routinely perform bony decompression alone in adults vs 8% in children. In 68% of adult cases, durotomy is performed routinely (46% of them leave the dura open, 54% perform a type of duroplasty) and 16% routinely resect the cerebellar tonsils. Only 17% leave the dura open in children. The most common indicators for durotomy are syringomyelia and intra-operative ultrasound findings. 61% believe there is equipoise/uncertainty in the optimal strategy for decompression and would be willing to participate in an RCT. Comments also mention the heterogeneity of CM1 and that treatment should be tailored to each patient. Conclusion: There is wide variation in pre- and intra-operative management of CM1 patients in the UK and the majority of neurosurgeons would be willing to participate in an RCT comparing bony decompression alone vs dural opening with/without duroplasty.

80. Heme Oxygenase-1 Gene promoter and associations with inflammation and subclinical vascular disease in Ugandan adolescents with and without HIV

Abstract Background Heme oxygenase-1 (HO-1) is a cytoprotective enzyme with potent anti-inflammatory, and anti-oxidant effects. The HO-1 response is modulated by functional polymorphisms (a dinucleotide (GT)n repeat length variation) in the HO-1 gene promoter region which have been associated with cardiovascular disease (CVD) susceptibility in adults. HO-1 polymorphisms and their associations with markers of inflammation and CVD in Ugandan adolescents with (HIV+) and without HIV (HIV-) have not been investigated. Methods We included 177 children (92 HIV+, 85 HIV-) enrolled in an ongoing observational cohort study at the Joint Clinical Research Center, Kampala, Uganda. All HIV+ participants were on ART. HO-1 (GT)n allele genotypes were determined by PCR of the (GT)n repeat region followed by fragment size determination on a capillary sequencer in DNA extracted from blood samples. Allele designations were assigned by number of (GT)n repeats: S &amp;lt; 27, M 27-34, or L &amp;gt; 34 repeats. We measured mean common carotid artery intima-media thickness (IMT) as a marker of CVD, markers of systemic inflammation (hsCRP, IL6, sTNFRI), monocyte activation (sCD14 and sCD163), and T-cell activation (expression of CD38 and HLA-DR on CD4+ and CD8+) , oxidized lipids, markers of gut integrity and fungal translocation (BDG). Results Median age (IQR) was 13 (11, 14), 44% were females, 86% had viral load &amp;lt; 20 copies/mL. 19% had a short allele genotype, 37% had a medium allele genotype and 44% had a long allele genotype (Figure). The shortest and longest allele length correlated with lower IMT in HIV- only (r=-0.36 and -0.30, respectively, p≤ 0.01 for both). Among biomarkers, only the medium allele correlated with oxidized lipids in HIV+ and with hsCRP and BDG in HIV- (p≤ 0.05). After adjusting for age, sex, and BMI, the presence of a long allele was associated with lower IMT. This was no longer significant after adjusting for markers of inflammation or oxidized lipids (Table). Heme Oxygenase-1 genotype allele length frequency in Ugandan cohort of HIV+ and HIV- youth 1: Models are adjusted for age (years), sex (male vs female), BMI (kg/m2) and HIV status (positive vs negative) 2: Models are adjusted for age (years), sex (male vs female), BMI (kg/m2), sCD14 (pg/mL) and HIV status (positive vs negative) 3: Models are adjusted for age (years), sex (male vs female), BMI (kg/m2), high sensitivity C reactive protein (ng/mL) and HIV status (positive vs negative) 4: Models are adjusted for age (years), sex (male vs female), BMI (kg/m2), oxidized lipids and HIV status (positive vs negative) Conclusion These findings underscore the potential of the HO pathways in modulating future risk for CVD in adolescents through inflammation. HIV status in this setting, likely influences the associations with the genotype with the risk of CVD. Further studies to validate our findings in this population are required. Disclosures Grace A. McComsey, MD, Gilead (Consultant, Advisor or Review Panel member)Janssen (Consultant, Advisor or Review Panel member)Merck (Consultant, Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member)Redhill (Research Grant or Support)Roche (Grant/Research Support)Tetraphase, Astellas (Research Grant or Support)Theratechnologies (Consultant)Vanda (Grant/Research Support)ViiV/GSK (Scientific Research Study Investigator, Advisor or Review Panel member)

1000. Serotype 3 pneumococci evade activation of the classical complement pathway

BackgroundComplement classical pathway (CCP) activation is the major mechanism leading to opsonophagocytic pneumococcal killing. Following immunization with 13-valent pneumococcal conjugate vaccine (PCV13), opsonophagocytic titers are lowest against serotype 3 among the 13 vaccine serotypes. Post licensure surveillance indicated early declines in serotype 3 invasive pneumococcal disease (IPD) were not sustained over time MethodsUsing flow cytometry, we measured C3 and C4 deposition on serotype 3 strains from children with IPD or nasopharyngeal [NP] carriage, and analyzed by clade. C4 deposition is an indicator of CCP, while C3 deposition is common to all complement pathways. We measured C3/C4 deposition on serotype 3 pneumococcal strains incubated with antibody depleted complement alone or with complement and the following antibodies: mouse monoclonal anti-capsular IgG or IgM, rabbit polyclonal serotype 3 antisera (IgG + IgM) [RPS3A] and RPS3A combined with anti-rabbit IgM, which blocks IgM function, leaving only polyclonal IgGResultsSerotype 3 strains demonstrated high variability in C3 binding when incubated with complement alone. RPS3A (containing both IgM+IgG) and monoclonal IgM activated CCP in all strains. Anti- serotype 3 monoclonal IgG and polyclonal IgG demonstrated absent or limited CCP activation; but activated alternative pathway in some strains. When analyzing complement deposition by clade, a lower proportion of clade II NP serotype 3 strains bound C3 when incubated with complement or monoclonal IgG, compared to clade Ia NP strains. Differences between clade Ia and II IPD strains were not apparent. ConclusionSerotype 3 strains did not demonstrate activation of the CCP in the presence IgG and varied in C3 deposition. Pneumococcal strains that evade CCP activation may be less sensitive to opsonophagocytosis. Our findings suggest a mechanism by which serotype 3 carriage and disease may persist despite immunization with conjugate vaccine containing serotype 3 polysaccharide.Disclosures Rotem Lapidot, MD MSCI, Pfizer (Consultant, Grant/Research Support, Advisor or Review Panel member) Mario Ramirez, PhD, GlaxoSmithKline (Advisor or Review Panel member)Merck Sharp & Dohme (Advisor or Review Panel member)Pfizer (Speaker’s Bureau) Ingrid L. Scully, PhD, Pfizer (Employee, Shareholder) Bradford D. Gessner, MD, MPH, Pfizer Inc. (Employee) stephen pelton, MD, Merck Vaccines (Advisor or Review Panel member, Research Grant or Support)Pfizer, Inc. (Consultant, Advisor or Review Panel member, Research Grant or Support)Sanofi pasteur (Advisor or Review Panel member, Research Grant or Support, DSMB)Seqirus (Consultant)

105. Impact of a Multiplex Polymerase Chain Reaction Panel on Duration of Empiric Antibiotic Therapy in Suspected Bacterial Meningitis

BackgroundMultiplex polymerase chain reaction (PCR) panels allow for rapid detection or exclusion of pathogens causing community-acquired meningitis and encephalitis (ME). However, the clinical impact of rapid multiplex PCR ME panel results on the duration of empiric antibiotic therapy is not well characterized.MethodsWe performed a retrospective pre-post study to evaluate the implementation of the FilmArray ME panel (BioFire Diagnostics, LLC) for diagnosis of bacterial meningitis at our institution. We included adults who presented with suspected bacterial meningitis, received empiric antibiotic therapy, and underwent cerebrospinal fluid microbiological testing in the emergency department. The primary outcome was duration of empiric antibiotic therapy. A bivariable analysis that compared baseline demographics, clinical characteristics, and study outcomes between the pre-ME panel and post-ME panel periods was performed using Mann-Whitney tests, chi-squared tests, or Fisher’s exact tests. Time-to-event analysis used the Kaplan-Meier method and log-rank statistics.ResultsIn the pre-ME panel period, the positive detection rate of bacterial pathogens was 2.2% (3/137) by cerebrospinal fluid culture and 4.3% (3/69) in the post-ME panel period. Table 1 shows baseline characteristics of patients. Compared to the pre-ME panel period, there were significant reductions in the post-ME panel period for the duration of empiric antibiotic therapy (median 34.7 h, IQR 8.5–61.7, vs. 12.3 h, IQR 3.3–40.0, P=0.01), time to targeted therapy (59.3 h, IQR 36.5–74.6, vs 7.02 h, IQR 0.9–12.4, P< 0.001), and hospital length of stay (4 d, IQR 2–7, vs. 3 d, IQR 1–5, P=0.03), as shown in Table 2. There was also significant reduction in time to discontinuation or de-escalation of empiric antibiotic therapy (P=0.049) as shown in Figure 1.Table 1. Baseline characteristics for patients with suspected bacterial meningitis Table 2. Antimicrobial use and hospitalization outcomes Compared to the pre-ME panel period, there were significant reductions in the post-ME panel period for the duration of empiric antibiotic therapy (P=0.01), time to targeted therapy (P<0.001), and hospital length of stay (P=0.03).Figure 1. Probability of Empiric Antibiotic Therapy Between Pre- and Post-ME Panel Periods Kaplan-Meier analysis of the time from initiation of empiric antibiotic therapy to discontinuation or de-escalation of empiric antibiotic therapy between the pre- and post-ME panel periods. P value from log-rank test=0.049 (n=206). There was a significant difference in the time to discontinuation or de-escalation of empiric antibiotic therapy between the groups (sex- and immunosuppressant use-adjusted hazard ratio, 1.46 [95% confidence interval, 1.08–1.97]; P=0.01).ConclusionThe implementation of the FilmArray ME panel for suspected bacterial meningitis appears to reduce the duration of empiric antibiotic therapy, time to targeted therapy, and hospital length of stay compared to traditional culture-based microbiological testing methods.Disclosures Justin J. Choi, MD, Allergan (Consultant, Grant/Research Support)Roche (Consultant, Grant/Research Support) Lars Westblade, PhD, Accelerate Diagnostics Inc (Grant/Research Support)BioFire Diagnostics (Grant/Research Support)Hardy Diagnostics (Grant/Research Support)Roche (Consultant, Advisor or Review Panel member)Shionogi Inc (Advisor or Review Panel member)Talis Biomedical (Advisor or Review Panel member) Marshall J. Glesby, MD, Enzychem (Consultant)Gilead (Grant/Research Support)ReAlta Life Sciences (Consultant)Regeneron (Consultant, Grant/Research Support)Sobi (Consultant)Springer (Other Financial or Material Support, Royalties)UpToDate (Other Financial or Material Support, Royalties)

18. An Easy-to-Implement Clinical-Trial Frailty Index Based on Accumulation of Deficits: Validation in Zoster Clinical Trials

BackgroundThe impact of frailty on the efficacy and safety of vaccines and therapeutic interventions is increasingly recognized, yet assessment of frailty in clinical trials is often considered logistically challenging. We developed the retrospective Clinical Trial Frailty Index (CT-FI), using baseline medical history and patient reported outcomes collected via standard instruments (Short Form Survey-36 and Euro Quality of Life-5 Dimension) in two clinical trials of the adjuvanted recombinant zoster vaccine (RZV, ZOE-50 [NCT01165177] and ZOE-70 [NCT01165229]). This post-hoc analysis aimed to show that CT-FI is a robust measure that may be used in any analysis where sufficient patient data has been collected in a clinical trial.MethodsItems included in the CT-FI were scored from 0 to 1, summed for each participant and divided by the total number of potential deficits. CT-FI was validated using descriptive methods verifying distribution and age- and sex-associations in relation to established FI characteristics, Cox regressions in relation to fatal outcomes hypothetically related to frailty, and re-sampling methods (Jackknife and Bootstrap procedures) within the FI to demonstrate robustness to inclusion/exclusion of specific individual variables.ResultsThe CT-FI distribution followed a gamma distribution with a range of 0 to 0.695; the distribution shifted to the right with age. The age-related slope of mean deficit accumulation per year increased with chronological age and was higher for women than men. The rate of mean deficit accumulation was 0.0025 for women vs 0.0016 for men < 70 years of age, and this increased to 0.0058 for women vs 0.0047 for men ≥70 years of age. In univariate and multivariate Cox regression survival analyses, FI, chronological age and sex were significant predictor factors for mortality. The Jackknife and Bootstrap re-sampling methods showed that the performance of CT-FI was not sensitive to inclusion/exclusion of specific individual or groups of variables, demonstrating the robustness of this methodology. ConclusionThe current analysis validates that CT-FI, an easy-to-implement FI, is a robust method which allows retrospective/prospective evaluation of clinical outcomes by frailty status in clinical trials.Disclosures Melissa K. Andrew, MD, PhD, GSK (Grant/Research Support)Pfizer (Grant/Research Support, Advisor or Review Panel member)Sanofi (Consultant, Grant/Research Support, Advisor or Review Panel member)Seqirus (Advisor or Review Panel member) Sean Matthews, MSc, GSK (Independent Contractor) Joon Hyung Kim, MD, GSK group of companies (Employee, Shareholder) Megan Riley, PhD, GSK group of companies (Employee, Shareholder) Desmond Curran, PhD, The GSK group of companies (Employee, Shareholder)

1408. Population-based Nontuberculous Mycobacteria Surveillance in Four Emerging Infections Program Sites, October 2019–March 2020

BackgroundNontuberculous mycobacteria (NTM) cause pulmonary (PNTM) and extrapulmonary (ENTM) disease. NTM infections are difficult to diagnose and treat; environmental exposures occur in both healthcare and community settings. Few population-based studies describe NTM disease epidemiology. Current data indicate PNTM disease and ENTM skin and soft tissue infections are increasing. We describe findings from a multi-site pilot of population-based NTM surveillance.MethodsCDC’s Emerging Infections Program conducted active, laboratory- and population-based surveillance for NTM cases occurring in 4 sites (Colorado [5 counties], Minnesota [2 counties], New York [2 counties], and Oregon [3 counties PNTM; statewide ENTM]) during October 1, 2019–March 31, 2020. PNTM cases were defined according to current published microbiologic criteria, based on isolation of NTM in respiratory cultures or tissue. ENTM cases required NTM isolation from a non-pulmonary specimen, excluding stool or rectal swabs. Demographic, clinical, exposure, and laboratory data were collected via medical record review. We calculated overall incidence per 100,000 population using census data and performed descriptive analyses of medical record data.ResultsOverall, 299 NTM cases were reported (231 [77%] PNTM); M. avium was the most commonly isolated species (Table). NTM incidence was 3.8 per 100,000 (PNTM 3.1/100,000; ENTM 0.7/100,000). Most patients with available data had ≥1 sign or symptom in the 14 days before culture (63 [97%] ENTM, 203 [92%] PNTM). During the surveillance period, 187 (63%) had their first infection-defining culture collected in an outpatient setting (33 [49%] ENTM, 154 [67%] PNTM). Of PNTM cases, 145 (64%) were female, and 154 (67%) had underlying pulmonary disease. Among ENTM cases, 29 (43%) were female, 9 (13%) had diabetes, 8 (12%) had HIV and 27 (40%) had infection at the site of a medical device or healthcare procedure. Common ENTM infection types were lymphadenitis (16 [24%]) and skin abscess (12 [18%]). Table. Characteristics of persons with NTM infection identified in population-based surveillance, October 1, 2019–March 31, 2020. ConclusionCharacterizing disease burden and affected populations with population-based NTM surveillance will provide data to inform potential interventions and monitor prevention strategy impact. Disclosures Christopher A. Czaja, MD, DrPH, Centers for Disease Control and Prevention (Grant/Research Support) Ruth Lynfield, MD, Nothing to disclose Ghinwa Dumyati, MD, Pfizer (Grant/Research Support)Roche Diagnostics (Advisor or Review Panel member) Emily Henkle, PhD, MPH, AN2 (Consultant, Advisor or Review Panel member)Zambon (Advisor or Review Panel member) Kevin L. Winthrop, MD, MPH, Insmed (Consultant, Grant/Research Support)Paratek (Consultant)RedHill (Consultant)Spero (Consultant) Kevin L. Winthrop, MD, MPH, Insmed (Consultant, Research Grant or Support)Paratek (Consultant)RedHill Biopharma (Consultant)Spero (Consultant)

192. Tolerability Outcomes of Multi-drug Antibiotic Treatment for Pulmonary Nontuberculous Mycobacterial Disease due to Mycobacterium avium Complex in U.S. Medicare Beneficiaries with Bronchiectasis

BackgroundNontuberculous mycobacteria (NTM), most frequently Mycobacterium avium complex (MAC), cause increasingly common pulmonary infections. Treatment interruptions and early discontinuation are common in MAC therapy, but population-based data on treatment outcomes are severely lacking. We examined tolerability outcomes of guideline-based 3-drug therapies (GBT) targeted for pulmonary MAC infection. MethodsAmong beneficiaries with bronchiectasis (ICD-9-CM 494.0 or 494.1) in U.S. Medicare data (01/2006 – 12/2014), we identified first-time MAC GBT therapy users, excluding those with cystic fibrosis, HIV, or a history of organ transplant. MAC GBT was defined as an overlapping prescription of ≥ 28-day supply of a macrolide, ethambutol and rifamycin. Using Cox regression methods, we compared time-to-regimen change or discontinuation within 12 months of therapy start in the following groups: 1) azithromycin-ethambutol-rifamycin vs. clarithromycin-ethambutol-rifamycin; 2) macrolide-ethambutol-rifampin vs. macrolide-ethambutol-rifabutin; and 3) azithromycin-ethambutol-rifampin vs. clarithromycin-ethambutol-rifabutin.ResultsWe identified 4,626 GBT therapy users (mean 77.9 years [s.d. 6.1], female [77.7%], and non-Hispanic white [87.2%]). Overall, the rate of regimen change or discontinuation was higher in the clarithromycin-based regimens compared to azithromycin-containing regimens, and in rifabutin-containing regimens compared to rifampin-containing regimens. The rate of drug regimen change or discontinuation was 65% greater in the clarithromycin-ethambutol-rifabutin group compared to the azithromycin-ethambutol-rifampin group (adjusted hazard ratio: 1.64, 95% CI: 1.43, 1.64) (Table 1, Figure 1). ConclusionAzithromycin-based regimens and rifampin-containing regimens were less likely to be changed or discontinued within 12 months of therapy compared to clarithromycin-based regimens and rifabutin-containing regimens, respectively. More research is needed to identify factors associated with early treatment change or discontinuation. Disclosures Emily Henkle, PhD, MPH, AN2 (Consultant, Advisor or Review Panel member)Zambon (Advisor or Review Panel member) Theodore K. Marras, MD, Astra Zeneca (Speaker’s Bureau)Insmed (Scientific Research Study Investigator)Novartis (Speaker’s Bureau)RedHill (Consultant)Spero (Consultant) Kevin L. Winthrop, MD, MPH, Insmed (Consultant, Grant/Research Support)Paratek (Consultant)RedHill (Consultant)Spero (Consultant) Kevin L. Winthrop, MD, MPH, Insmed (Consultant, Research Grant or Support)Paratek (Consultant)RedHill Biopharma (Consultant)Spero (Consultant)

937. A Clinical Prediction Tool to Determine Risk of Infection in the First Year Following Heart Transplant

BackgroundInvasive infection is a dangerous complication of heart transplant (HT). No objectively-defined set of risk factors has been established which can reliably predict infection in this population. The aim of this study was to develop a clinical prediction model for use at one month post-HT with the ability to predict serious infection in the first year.MethodsA retrospective cohort study of all HT recipients at a single center between 2000 and 2018 was performed, excluding dual-organ recipients, those who died within one month of HT, and those with insufficient data. The composite endpoint included cytomegalovirus infection (CMV), herpes simplex (HSV) or varicella zoster virus infection (VZV), blood stream infection (BSI), and invasive fungal infection (IFI). The follow-up period extended from 1 month to 1 year post-HT. A least absolute shrinkage and selection operator (LASSO) regression model was fit using 13 candidate variables. A C-statistic, calibration curve, and Brier score were used to assess model performance.Results375 patients were analyzed; 93 outcomes occurred (65 CMV, 3 HSV, 2 VZV, 28 BSI, and 15 IFI). 12 of 13 variables remained in the final model: year of transplant, age at transplant, ischemic cardiomyopathy, diabetes, immune-mediating disease, need for renal replacement therapy in first month, CMV risk status (high, intermediate, low) derived from donor-recipient serology, use of basiliximab induction, use of cytolytic agent in first month, use of ritixumab in first month, rejection treated with high-dose steroids in first month, lymphocyte count under 0.75 x103cells/µL at 1 month, and inpatient status at 1 month. The C-statistic was 0.82 and Brier score 0.142. The calibration curve is shown in Figure 1. Figure 1. Calibration plot Actual versus predicted probability of infection by 1 year. Gray line = ideal Dotted line = smoothed non-parametric calibration curveConclusionThis model synthesizes multiple highly-relevant clinical and laboratory parameters, available at 1 month post-HT, into a unified, objective, and clinically-useful prediction tool for the occurrence of serious infection in the first post-transplant year. Good discrimination and calibration are demonstrated. External validation is required before generalized use.Disclosures Jennifer Chow, M.D., M.S., Merck (Grant/Research Support)Takeda (Grant/Research Support) David R. Snydman, MD, Merck (Consultant, Advisor or Review Panel member, Research Grant or Support)Takeda (Shire) (Advisor or Review Panel member)