Building Affordable, Durable, Medium-fidelity Ballistic Gel Phantoms for Ultrasound-guided Nerve Block Training.

Ultrasound phantoms - alternatives to live human tissue - give learners the opportunity to practice ultrasound-guided regional anesthesia without introducing undue risk to patients. Gelatin-based phantoms provide educators with durable and reusable task trainers; however, commercially available gel-based phantoms are expensive. Here, we investigate the production of durable, low-cost, ballistic gel-based ultrasound phantoms for median, femoral, suprainguinal fascia iliaca plane, and serratus anterior plane nerve blocks, as well as a methodology for producing a phantom for any ultrasound-guided nerve block procedure. Computer-aided design (CAD) software was utilized to design four phantoms replicating the anatomy of median, femoral, suprainguinal fascia iliaca plane, and serratus anterior plane nerve blocks, including relevant landmarks and tissue planes. Plastic models of the desired tissue planes were 3D printed and used to create silicone molds. Ballistic gel was melted and mixed with flour and dye to create a liquid, echogenic ballistic gel, which was poured into the silicone molds. Vessels were simulated by creating negative space in the ballistic gel using metal rods. Nerves were simulated using yarn submerged in ultrasound gel. Simulated bones were designed using CAD and 3D printed. Ballistic gel is a versatile, durable medium that can be used to simulate a variety of tissues and can be melted and molded into any shape. Under ultrasound, these phantoms provide realistic tissue planes that represent the borders between different layers of skin, muscle, and fascia. The echogenicity of the muscle tissue layers, nerves, vessels, and bones is realistic, and bones have significant posterior shadowing as would be observed in a human subject. These phantoms cost $200 each for the first phantom and $60 for each subsequent phantom. These phantoms require some technical skill to design, but they can be built for just 4% of the cost of their commercial counterparts.

Improving Traditional Registrational Trial End Points: Development and Application of a Desirability of Outcome Ranking End Point for Complicated Urinary Tract Infection Clinical Trials.

BACKGROUND: Traditional end points used in registrational randomized, controlled trials (RCTs) often do not allow for complete interpretation of the full range of potential clinical outcomes. Desirability of outcome ranking (DOOR) is an approach to the design and analysis of clinical trials that incorporates benefits and risks of novel treatment strategies and provides a global assessment of patient experience. METHODS: Through a multidisciplinary committee of experts in infectious diseases, clinical trial design, drug regulation, and patient experience, we developed a DOOR end point for infectious disease syndromes and demonstrated how this could be applied to 3 registrational drug trials (ZEUS, APEKS-cUTI, and DORI-05) for complicated urinary tract infections (cUTIs). ZEUS compared fosfomycin to piperacillin/tazobactam, APEKS-cUTI compared cefiderocol to imipenem, and DORI-05 compared doripenem to levofloxacin. Using DOOR, we estimated the probability of a more desirable outcome with each investigational antibacterial drug. RESULTS: In each RCT, the DOOR distribution was similar and the probability that a patient in the investigational arm would have a more desirable outcome than a patient in the control arm had a 95% confidence interval containing 50%, indicating no significant difference between treatment arms. DOOR facilitated improved understanding of potential trade-offs between clinical efficacy and safety. Partial credit and subgroup analyses also highlight unique attributes of DOOR. CONCLUSIONS: DOOR can effectively be used in registrational cUTI trials. The DOOR end point presented here can be adapted for other infectious disease syndromes and prospectively incorporated into future clinical trials.

Lefamulin in Patients with Community-Acquired Bacterial Pneumonia Caused by Atypical Respiratory Pathogens: Pooled Results from Two Phase 3 Trials.

Lefamulin was the first systemic pleuromutilin antibiotic approved for intravenous and oral use in adults with community-acquired bacterial pneumonia based on two phase 3 trials (Lefamulin Evaluation Against Pneumonia [LEAP]-1 and LEAP-2). This pooled analysis evaluated lefamulin efficacy and safety in adults with community-acquired bacterial pneumonia caused by atypical pathogens (Mycoplasma pneumoniae, Legionella pneumophila, and Chlamydia pneumoniae). In LEAP-1, participants received intravenous lefamulin 150 mg every 12 h for 5-7 days or moxifloxacin 400 mg every 24 h for 7 days, with optional intravenous-to-oral switch. In LEAP-2, participants received oral lefamulin 600 mg every 12 h for 5 days or moxifloxacin 400 mg every 24 h for 7 days. Primary outcomes were early clinical response at 96 ± 24 h after first dose and investigator assessment of clinical response at test of cure (5-10 days after last dose). Atypical pathogens were identified in 25.0% (91/364) of lefamulin-treated patients and 25.2% (87/345) of moxifloxacin-treated patients; most were identified by ≥1 standard diagnostic modality (M. pneumoniae 71.2% [52/73]; L. pneumophila 96.9% [63/65]; C. pneumoniae 79.3% [46/58]); the most common standard diagnostic modality was serology. In terms of disease severity, more than 90% of patients had CURB-65 (confusion of new onset, blood urea nitrogen > 19 mg/dL, respiratory rate ≥ 30 breaths/min, blood pressure <90 mm Hg systolic or ≤60 mm Hg diastolic, and age ≥ 65 years) scores of 0-2; approximately 50% of patients had PORT (Pneumonia Outcomes Research Team) risk class of III, and the remaining patients were more likely to have PORT risk class of II or IV versus V. In patients with atypical pathogens, early clinical response (lefamulin 84.4-96.6%; moxifloxacin 90.3-96.8%) and investigator assessment of clinical response at test of cure (lefamulin 74.1-89.7%; moxifloxacin 74.2-97.1%) were high and similar between arms. Treatment-emergent adverse event rates were similar in the lefamulin (34.1% [31/91]) and moxifloxacin (32.2% [28/87]) groups. Limitations to this analysis include its post hoc nature, the small numbers of patients infected with atypical pathogens, the possibility of PCR-based diagnostic methods to identify non-etiologically relevant pathogens, and the possibility that these findings may not be generalizable to all patients. Lefamulin as short-course empiric monotherapy, including 5-day oral therapy, was well tolerated in adults with community-acquired bacterial pneumonia and demonstrated high clinical response rates against atypical pathogens.

Candidate Quality Measures for Orthopaedic Surgery Outreach Trips: A Systematic Review.

INTRODUCTION: Up to 30% of the global burden of disease is secondary to surgical conditions, most of which falls on those in low- and middle-income countries (LMICs). Ensuring that the quality of care delivered during outreach trips to address these conditions is foundational. Limited work has been done to develop and implement tools to assess and improve the quality of care for these trips. The purpose of this study was to identify candidate quality measures that address orthopaedic surgery outreach trips in LMICs. METHODS: We conducted a systematic review of MEDLINE/PubMed, EMBASE, Web of Science, Google Scholar, and other databases to identify candidate quality measures relevant to orthopaedic surgery outreach to LMICs. Quality measures were then categorized by system management, sustainability, or both system management and sustainability according to the framework and structures, processes, and outcomes of Bido et al according to the Donabedian domains. RESULTS: Our initial search yielded 3,891 articles, 22 of which met the inclusion criteria. Seventy-nine candidate quality measures were identified. Regarding the framework of Bido et al, 55 of 79 (70%) were related to system management, 8 (10%) were related to sustainability, and 16 (20%) were related to both system management and sustainability. According to Donabedian domains, 43 of 79 (54%) were structure measures, 25 (32%) were process measures, and 11 (14%) were outcome measures. DISCUSSION: Quality measures addressing orthopaedic surgery outreach trips are lacking in quantity and breadth, limiting the ability to assess and improve the safety and quality of care provided. The candidate quality measures identified disproportionately focus on systems management and structures, with few related to sustainability and few addressing outcomes. Patients receiving care on outreach trips would benefit from the implementation of the measures identified in this review and from the development of quality measures that capture all domains of care and emphasize outcomes. LEVEL OF EVIDENCE: Level III.

Oral 5-Day Lefamulin for Outpatient Management of Community-Acquired Bacterial Pneumonia: Post-hoc Analysis of the Lefamulin Evaluation Against Pneumonia (LEAP) 2 Trial.

BACKGROUND: Safe and effective oral antibiotics are needed for outpatient management of moderate to severe community-acquired bacterial pneumonia (CABP). OBJECTIVE: We describe a post-hoc analysis of adults with CABP managed as outpatients from the Lefamulin Evaluation Against Pneumonia (LEAP) 2 double-blind, noninferiority, phase 3 clinical trial. METHODS: LEAP 2 compared the efficacy and safety of oral lefamulin 600 mg every 12 h (5 days) vs. oral moxifloxacin 400 mg every 24 h (7 days) in adults (inpatients and outpatients) with Pneumonia Outcomes Research Team (PORT) risk classes II‒IV. RESULTS: Overall, 41% (151 of 368) of patients receiving lefamulin and 43% (159 of 368) of patients receiving moxifloxacin started treatment as outpatients-44% and 40%, respectively, were PORT risk class III/IV, and 21% in both groups had CURB-65 scores of 2‒3. Early clinical response (at 96 ± 24 h) and investigator assessment of clinical response success rates at test of cure (5‒10 days after last study drug dose) were high and similar in both groups among all (lefamulin, 91% vs. moxifloxacin, 89‒90%), PORT risk class III/IV (89‒91% vs. 88‒91%), and CURB-65 score 2‒3 (87‒90% vs. 82‒88%) outpatients. Few outpatients (lefamulin, 2.6%; moxifloxacin, 2.5%) discontinued the study drug because of treatment-emergent adverse events (TEAEs). No outpatient in the lefamulin group was hospitalized for a TEAE, compared with 5 patients (3%), including two deaths, in the moxifloxacin group. CONCLUSIONS: These data suggest that 5 days of oral lefamulin can be given in lieu of fluoroquinolones for outpatient treatment of adults with CABP and PORT risk class III/IV or CURB-65 scores of 2‒3.

Does a Question Prompt List Improve Perceived Involvement in Care in Orthopaedic Surgery Compared with the AskShareKnow Questions? A Pragmatic Randomized Controlled Trial.

BACKGROUND: Most conditions in orthopaedic surgery are preference-sensitive, where treatment choices are based on the patient's values and preferences. One set of tools increasingly used to help align treatment choices with patient preferences are question prompt lists (QPLs), which are comprehensive lists of potential questions that patients can ask their physicians during their encounters. Whether or not a comprehensive orthopaedic-specific question prompt list would increase patient-perceived involvement in care more effectively than might three generic questions (the AskShareKnow questions) remains unknown; learning the answer would be useful, since a three-question list is easier to use compared with the much lengthier QPLs. QUESTION/PURPOSE: Does an orthopaedic-specific question prompt list increase patient-perceived involvement in care compared with the three generic AskShareKnow questions? METHODS: We performed a pragmatic randomized controlled trial of all new patients visiting a multispecialty orthopaedic clinic. A pragmatic design was used to mimic normal clinical care that compared two clinically acceptable interventions. New patients with common orthopaedic conditions were enrolled between August 2019 and November 2019 and were randomized to receive either the intervention QPL handout (orthopaedic-specific QPL with 45 total questions, developed with similar content and length to prior QPLs used in hand surgery, oncology, and palliative care) or a control handout (the AskShareKnow model questions, which are: "What are my options? What are the benefits and harms of those options? How likely are each of those benefits and harms to happen to me?") before their visits. A total of 156 patients were enrolled, with 78 in each group. There were no demographic differences between the study and control groups in terms of key variables. After the visit, patients completed the Perceived Involvement in Care Scale (PICS), a validated instrument designed to evaluate patient-perceived involvement in their care, which served as the primary outcome measure. This instrument is scored from 0 to 13, with higher scores indicating higher perceived involvement. RESULTS: There was no difference in mean PICS scores between the intervention and control groups (QPL 8.3 ± 2.3, control 8.5 ± 2.3, mean difference 0.2 [95% CI -0.53 to 0.93 ]; p = 0.71. CONCLUSION: In patients undergoing orthopaedic surgery, a QPL does not increase patient-perceived involvement in care compared with providing patients the three AskShareKnow questions. Implementation of the three AskShareKnow questions can be a more efficient way to improve patient-perceived involvement in their care compared with a lengthy QPL. LEVEL OF EVIDENCE: Level II, therapeutic study.

Development of a Needs Assessment Tool to Promote Capacity Building in Hand Surgery Outreach Trips: A Methodological Triangulation Approach.

PURPOSE: The surgical burden in low- and middle-income countries (LMIC) is immense. Despite the increase in resources invested in surgical outreach trips to LMIC, there is no consistent process for understanding the needs of the site and for preparing the necessary resources to deliver care. Given the importance and lack of a comprehensive and standardized needs assessment tool, we aimed to create a tool that assesses the needs and capacity of a site to inform site selection and expectations and improve quality of care. METHODS: We used methodological triangulation, a technique that incorporates multiple and different types of data collection methods to study a phenomenon. We used 2 standardized World Health Organization (WHO) tools to develop a hand surgery-specific needs assessment tool. We then identified missing items and made refinements as a result of field testing at 2 facilities and qualitative analysis of semistructured interviews of hand surgeons with international outreach experience. Interviews were coded and analyzed using conductive content analysis. Key concepts explored included domains and subdomains pertaining to essential considerations prior to a hand surgery outreach trip. RESULTS: Current generic needs assessment tools do not capture all necessary domains and subdomains for a hand surgery outreach trip. The WHO tools provide a framework for reference and foundation; field testing and qualitative interviews identified hand surgery-specific items. We developed a tool that includes 7 domains: (1) human resources; (2) physical resources; (3) procedures; (4) cultural and language barriers; (5) safety, quality, and access; (6) regulation and cost; and (7) knowledge transfer and teaching and associated subdomains relevant to hand surgery. CONCLUSIONS: A hand surgery-specific standardized needs assessment tool may ensure appropriate resources and personnel are deployed for outreach trips to improve site selection, expectation setting, and quality of care. CLINICAL RELEVANCE: A needs assessment tool is a standardized, comprehensive tool to assess the needs and capacity of a new site prior to hand surgery outreach trips to improve site selection, expectation setting, and delivery of high-quality, safe, and effective care in LMIC.

Safe Travel Preparation for HIV-Infected Patients.

PURPOSE OF REVIEW: Infectious diseases are a risk when traveling internationally, and it is important to know the potential disease burden of a region and take appropriate preventative actions before traveling. For individuals with HIV, there are special considerations and contradictions for various vaccines and medications as well as interactions with likely antiviral drugs. The purpose of this review is to summarize the vaccine and medication recommendations for travelers with HIV infection. We also review recent studies to update these recommendations. RECENT FINDINGS: The recommendation for yellow fever vaccine has changed in June of 2016, and it is now a once in a lifetime vaccine instead of being given every 10 years. A new cholera vaccine, Vaxchora™ was approved in 2016. Since it is a live vaccine, its impact on immunocompromised individuals is still not fully known. A recent study found that immunocompromised patients responded well to the hepatitis A vaccine, although acquiring immunity may take longer than in non-immunocompromised people. There are some new anti-viral medicines that need to be considered with interactions for other travel medicines, in particular, the anti-malaria drugs. This review provides current knowledge on how HIV-infected and immunocompromised persons respond to medications and vaccines for prevention of infectious diseases in travelers. These recommendations will be useful to recommend safer travel for the HIV-infected patient. Some newer vaccines and medications will need further evaluation and assessment to determine safety and impact on HIV-positive travelers.

Feasibility of home infusion and self-administration of nanofiltered C1 esterase inhibitor for routine prophylaxis in patients with hereditary angioedema and characterization of a training and support program.

Hereditary angioedema (HAE) is a rare, chronic disease of C1 inhibitor deficiency. Study researchers evaluated the prevalence of home and self-administration of nanofiltered, human-derived C1 esterase inhibitor infusions and the implementation of a nursing training and support program. Home administration rate increased from 49.0% to 75.8%. The percentage who self-administered increased from 20.3% to 43.9%. Doses per week averaged 1.85 at home compared with 1.40 in infusion centers and physicians' offices. Patients required an average of 5 visits to be trained. Self-administration is a viable, feasible option in the management of HAE, which is facilitated by a nurse-managed training and support program.