Yttrium-90 Anti-CD25-BEAM-Conditioning for Autologous Hematopoietic Cell Transplantation in Peripheral T Cell Lymphoma.

Peripheral T cell lymphomas (PTCL) have a poor prognosis with current treatments. High-dose chemotherapy followed by autologous hematopoietic cell transplant (AHCT) is used as a consolidation strategy after achieving clinical remission with first-line therapy, as well as in chemosensitive relapse if allogeneic transplant is not an option. CD25 is a targetable protein often highly expressed in PTCL. In this phase 1 clinical trial, we tested the addition of beta-emitting 90Y-labeled chimeric anti-CD25 basiliximab (aTac) to BEAM (carmustine, etoposide, cytarabine, melphalan) as conditioning for AHCT in patients with PTCL. Twenty-three AHCT-eligible patients were enrolled, and 20 received therapeutic 90Y-aTac-BEAM AHCT. Radiation doses of 0.4, 0.5 and 0.6 mCi/kg were tested. With no observed dose-limiting toxicities, 0.6 mCi/kg was deemed the recommended phase 2 dose. The most prevalent adverse effect, grade 2 mucositis, was experienced by 80% of patients. As of this report, 6 (30%) of the treated patients had died, 5 due to progressive disease and 1 due to multiple organ failure [median time of death 17 mo (range: 9-21 mo)] post-AHCT. Median follow-up was 24 mo (range: 9-26 mo) overall and 24 mo (range: 13-26 mo) for surviving patients. For patients who received therapeutic 90Y-aTac-BEAM AHCT, the 2-year progression-free and overall survival were 59% (95% CI: 34-77%) and 68% (95% CI: 42-84%), respectively. 90Y-aTac-BEAM appears to be safe as an AHCT conditioning regimen for PTCL, with no increased toxicity over the toxicities historically seen with BEAM alone in this patient population. This trial was registered at www.clinicaltrials.gov as # NCT02342782.

Psychological distress and PTSD among clinicians in Roma, Lesotho during the COVID-19 pandemic.

BACKGROUND:  Since 2020, the world has been battling the coronavirus disease 2019 (COVID-19) pandemic. The mortality and morbidity at the height of the pandemic sparked generalised fear and uncertainty about the future. Concerns were raised about the psychological impact of the pandemic on workers in healthcare systems globally. This study was conducted to establish the degree of psychological impact of the pandemic on frontline health workers in Lesotho. METHODS:  The study used a quantitative cross-sectional survey design. The Kessler psychological distress screening tool (K-10) and the post-traumatic stress disorder (PTSD) checklist for civilians (PCL-C) were administered to screen for psychological distress among clinical staff at St. Joseph's Hospital in Roma and its four Health Centres. Additional open- and closed-ended questions were added for context. Data were analysed using Fisher's exact tests, Pearson chi-square tests and correlation studies. RESULTS:  Of the 101 participants, 42 (41.6%) scored ≥ 24 on the K-10 scale (95% CI: 32.0% - 51.2%) indicating moderate to severe psychological distress and 32 (31.7%) scored ≥ 50 on the PCL-C checklist suggesting severe PTSD (95% CI: 24.5% - 42.9%). High scores on the K-10 were found more among men than women (17 [37.8%] vs. 4 [7.1%]; p ≤ 0.001). Post-traumatic stress disorder was more in the younger age group (p ≤ 0.03), in those reporting anxiety (p = 0.005) and those with more co-morbidities (p ≤ 0.001). CONCLUSION:  This study revealed the grave psychological impact of the COVID-19 pandemic on frontline clinical health workers in Lesotho.Contribution: These data will assist health leaders and policymakers to implement mental health support interventions for health workers in future.

Eutectic mixture of local anesthetics and amethocaine as topical anesthetics in pediatrics: a meta-analysis.

BACKGROUND: Pediatric patients often receive topical anesthesia before skin procedures in the Emergency Department, with EMLA cream and amethocaine gel being common choices. The most effective option remains a subject of debate. OBJECTIVE: Our goal was to compare EMLA cream with amethocaine gel in pediatric patients undergoing topical anesthesia, focusing on outcomes: first-attempt cannulation success, child-reported visual analogue scale (VAS) score, parent-reported VAS score, observed pain score, child-reported absence of pain, and child-reported acceptable anesthesia. METHODS: A database search for studies comparing EMLA cream and amethocaine gel in pediatric topical anesthesia was conducted. Two reviewers extracted and cross-verified data, with a third ensuring accuracy. Using R software, a pairwise meta-analysis was performed via the Mantel-Haenszel method. Outcomes were pooled as risk ratios or standard mean differences with 95% confidence intervals using the random-effects model. RESULTS: Amethocaine gel surpasses EMLA cream in child-reported pain absence and first cannulation success. No significant differences were found in child-reported acceptable anesthesia or observed pain scores. Similarly, child- and parent-reported VAS scores showed no variations between EMLA and amethocaine. CONCLUSION: This analysis favors amethocaine gel for pediatric topical anesthesia. Further large randomized trials comparing EMLA cream and amethocaine gel in pediatric patients are warranted. IMPACT: Procedural pain is a major concern for pediatric patients, their families, and physicians. Topical anesthesia is routinely given prior to children undergoing skin-related procedures in the Emergency Department. In pediatric patients, topical anesthetics such as eutectic mixture of local anesthetics cream and amethocaine gel have proved to be pioneering in pain reduction, but the most effective method is often disputed. Presently, this is the most comprehensive pooled analysis of trials comparing EMLA cream and amethocaine gel in pediatric patients undergoing topical anesthesia. Amethocaine performed better with regards to child-reported absence of pain and first attempt cannulation success.

Redirecting raltitrexed from cancer cell thymidylate synthase to Mycobacterium tuberculosis phosphopantetheinyl transferase.

There is a compelling need to find drugs active against Mycobacterium tuberculosis (Mtb). 4'-Phosphopantetheinyl transferase (PptT) is an essential enzyme in Mtb that has attracted interest as a potential drug target. We optimized a PptT assay, used it to screen 422,740 compounds, and identified raltitrexed, an antineoplastic antimetabolite, as the most potent PptT inhibitor yet reported. While trying unsuccessfully to improve raltitrexed's ability to kill Mtb and remove its ability to kill human cells, we learned three lessons that may help others developing antibiotics. First, binding of raltitrexed substantially changed the configuration of the PptT active site, complicating molecular modeling of analogs based on the unliganded crystal structure or the structure of cocrystals with inhibitors of another class. Second, minor changes in the raltitrexed molecule changed its target in Mtb from PptT to dihydrofolate reductase (DHFR). Third, the structure-activity relationship for over 800 raltitrexed analogs only became interpretable when we quantified and characterized the compounds' intrabacterial accumulation and transformation.

Predicting future occlusion or stenosis of lower extremity bypass grafts using artificial intelligence to simultaneously analyze all flow velocities collected in current and previous ultrasound examinations.

Objective: Routine surveillance with duplex ultrasound (DUS) examination is recommended after femoral-popliteal and femoral-tibial-pedal vein bypass grafts with various intervals postoperatively. The presently used methodology to analyze bypass graft DUS examination does not use all the available data and has been shown to have a significant rate for missing impending bypass graft failure. The objective of this research is to investigate recurrent neural networks (RNNs) to predict future bypass graft occlusion or stenosis. Methods: This study includes DUS examinations of 663 patients who had bypass graft operations done between January 2009 and June 2022. Only examinations without missing values were included. We developed two RNNs (a bidirectional long short-term memory unit and a bidirectional gated recurrent unit) to predict bypass graft occlusion and stenosis based on peak systolic velocities collected in the 2 to 5 previous DUS examinations. We excluded the examinations with missing values and split our data into training and test sets. Then, we applied 10-fold cross-validation on training to optimize the hyperparameters and compared models using the test data. Results: The bidirectional long short-term memory unit model can gain an overall sensitivity of 0.939, specificity of 0.963, and area under the curve of 0.950 on the prediction of bypass graft occlusion, and an overall sensitivity of 0.915, specificity of 0.909, and area under the curve of 0.912 predicting the development of a future critical stenosis. The results on different bypass types show that the system performs differently on different types. The results on subcohorts based on gender, smoking status, and comorbidities show that the performance on current smokers is lower than the never smoker. Conclusions: We found that RNNs can gain good sensitivity, specificity, and accuracy for the detection of impending bypass graft occlusion or the future development of a critical bypass graft stenosis using all the available peak systolic velocity data in the present and previous bypass graft DUS examinations. Integrating clinical data, including demographics, social determinants, medication, and other risk factors, together with the DUS examination may result in further improvements. Clinical Relevance: Detecting bypass graft failure before it occurs is important clinically to prevent amputations, salvage limbs, and save lives. Current methods evaluating screening duplex ultrasound examinations have a significant failure rate for detecting a bypass graft at risk for failure. Artificial intelligence using recurrent neural networks has the potential to improve the detection of at-risk bypass graft before they fail. Additionally, artificial intelligence is in the news and is being applied to many fields. Vascular surgeons need to know its potential to improve vascular outcomes.

Minimally invasive, surgical, and transcatheter aortic valve replacement: A network meta-analysis.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has evolved as an alternative to surgical aortic valve replacement (SAVR). In addition to full-sternotomy (FS), recent reports have shown successful minimally-invasive SAVR approaches, including mini-sternotomy (MS) and mini-thoracotomy (MT). This network-meta-analysis (NMA) seeks to provide an outcomes comparison based on these different modalities (MS, MT, TAVR) compared with FS as a reference arm for the management of aortic valve disease. METHODS: A comprehensive literature search was performed to identify studies that compared minimally-invasive SAVR (MS/MT) to conventional FS-SAVR, and/or TAVR. Bayesian NMA was performed using the random effects model. Outcomes were pooled as risk ratios (RR) with their 95 % confidence intervals (CIs). Our primary outcomes included 30-day mortality, stroke, acute kidney injury (AKI), major bleeding, new permanent pacemaker (PPM), and paravalvular leak (PVL). We also assessed long-term mortality at the latest follow-up. RESULTS: A total of 27,117 patients (56 studies) were included; 10,397 patients had FS SAVR, 9523 had MS, 5487 had MT, and 1710 had TAVR. Compared to FS, MS was associated with statistically-significantly lower rates of 30-day mortality (RR, 0.76, 95%CI 0.59-0.98), stroke (RR, 0.84, 95%CI 0.72-0.97), AKI (RR, 0.76, 95%CI 0.61-0.94), and long-term mortality (RR 0.84, 95%CI 0.72-0.97) at a weighted mean follow-up duration of 10.4 years, while MT showed statistically-significantly higher rates of 30-day PVL (RR, 3.76, 95%CI 1.31-10.85) and major bleeding (RR 1.45; 95%CI 1.08-1.94). TAVR had statistically significant lower rates of 30-day AKI (RR 0.49, 95%CI 0.31-0.77), but showed statistically-significantly higher PPM (RR 2.50; 95%CI 1.60-3.91) and 30-day PVL (RR 12.85, 95%CI 5.05-32.68) compared to FS. CONCLUSIONS: MS was protective against 30-day mortality, stroke, AKI, and long-term mortality compared to FS; TAVR showed higher rates of 30-day PVL and PPM but was protective against AKI. Conversely, MT showed higher rates of 30-day PVL and major bleeding. With the emergence of TAVR, the appropriate benchmarks for SAVR comparison in future trials should be the minimally-invasive SAVR approaches to provide clinical equipoise.

Bioprosthetic versus mechanical valves for mitral valve replacement in patients < 70 years: an updated pairwise meta-analysis.

BACKGROUND: The ideal conduit for mitral valve replacement (MVR) remains elusive, particularly among younger patients due to increased life expectancy. We perform a pairwise meta-analysis comparing the use of bioprosthetic valves (BPV) and mechanical mitral valves (MMV) in patients < 70 years old undergoing MVR. METHODS: We comprehensively searched medical databases to identify studies comparing the use of BPV and MMV in patients < 70 years old undergoing MVR. Pairwise meta-analysis was performed using the Mantel-Haenszel method in R version 4.0.2. Outcomes were pooled using the random effect model as risk ratios (RR) with their 95% confidence intervals (95% CI). RESULTS: 16,879 patients from 15 studies were pooled. Compared to MMV, BPV was associated with significantly higher rates of 30-day mortality (RR 1.53, p = 0.0006) but no difference in 30-day stroke (RR 0.70, p = 0.43). At a weighted mean follow-up duration of 14.1 years, BPV was associated with higher rates of long-term mortality (RR 1.28, p = 0.0054). No difference was seen between the two groups for risk of long-term stroke (RR 0.92, p = 0.67), reoperation(RR 1.72, p = 0.12), or major-bleeding (RR 0.57, p = 0.10) at a weighted mean follow-up duration of 11.7, 11.3, and 11.9 years, respectively. CONCLUSION: The use of MMV in patients < 70 undergoing MVR is associated with lower rates of 30-day/long-term mortality compared to BPV. No significant differences were observed for risk of 30-day/long-term stroke, long-term reoperation, and long-term major bleeding. These findings support the use of MMV in younger patients, although prospective, randomized trials are still needed.

Complete genome sequences of cluster G1 and cluster K4 Mycobacterium smegmatis phages omnicritical and Barkley26.

We present the complete genome sequence of two Actinobacteriophages, OmniCritical and Barkley26, isolated in Clark County, NV. Over two semesters, The University of Nevada, Las Vegas (UNLV) students isolated and purified phages and manually annotated the genomes. The courses follow the HHMI Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Sciences (SEA-PHAGES) curricula.

Unicompartmental knee arthroplasty revised to total knee arthroplasty versus primary total knee arthroplasty: A meta-analysis of matched studies.

BACKGROUND: Unicompartmental knee arthroplasty (UKA) offers a less invasive alternative to total knee arthroplasty (TKA), but is accompanied by a high revision risk. The aim of our study was to perform a meta-analysis comparing outcomes of UKA revised to TKA versus primary TKA, to assess if UKA is an effective treatment option, despite its potential need for revision. METHODS: Studies comparing matched cohorts of patients with UKA revised to TKA versus primary TKA were identified via the PubMed, Ovid EMBASE, and Scopus databases. The following outcome measures were compared between treatment modalities: postoperative reoperation or revision, total complications, range of motion, patient-reported outcome measures, and length of stay. RESULTS: Ten studies were included with 1,070 patients: 410 UKA to TKA and 660 primary TKA. At an average follow-up of 5.6 years in the UKA to TKA cohort and 5.7 years in the primary TKA cohort, there were no significant difference in risk of revision (p = 0.81), total complications (p = 0.54), range of motion (p = 0.09), or length of stay (p = 0.31). Both objective and functional Knee Society Score were significantly higher in patients with primary TKA (p < 0.01). However, there was no difference in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) or pain scores (p = 0.13 and p = 0.21, respectively). CONCLUSION: UKA revised to TKA produced comparable clinical and patient-reported outcomes to a primary TKA. UKA may be an effective treatment option in unicompartmental arthritis that would allow for improved functionality and satisfaction without the concern of outcomes deteriorating in patients where a revision becomes necessary.

Daily Summer Temperatures and Hospitalization for Acute Cardiovascular Events: Impact of Outdoor PM 2.5 Oxidative Potential on Observed Associations Across Canada.

BACKGROUND: Oxidative stress plays an important role in the health impacts of both outdoor fine particulate air pollution (PM 2.5 ) and thermal stress. However, it is not clear how the oxidative potential of PM 2.5 may influence the acute cardiovascular effects of temperature. METHODS: We conducted a case-crossover study of hospitalization for cardiovascular events in 35 cities across Canada during the summer months (July-September) between 2016 and 2018. We collected three different metrics of PM 2.5 oxidative potential each month in each location. We estimated associations between lag-0 daily temperature (per 5ºC) and hospitalization for all cardiovascular (n = 44,876) and ischemic heart disease (n = 14,034) events across strata of monthly PM 2.5 oxidative potential using conditional logistical models adjusting for potential time-varying confounders. RESULTS: Overall, associations between lag-0 temperature and acute cardiovascular events tended to be stronger when outdoor PM 2.5 oxidative potential was higher. For example, when glutathione-related oxidative potential (OP GSH ) was in the highest tertile, the odds ratio (OR) for all cardiovascular events was 1.040 (95% confidence intervals [CI] = 1.004, 1.074) compared with 0.980 (95% CI = 0.943, 1.018) when OP GSH was in the lowest tertile. We observed a greater difference for ischemic heart disease events, particularly for older subjects (age >70 years). CONCLUSIONS: The acute cardiovascular health impacts of summer temperature variations may be greater when outdoor PM 2.5 oxidative potential is elevated. This may be particularly important for ischemic heart disease events.

Minimally Invasive Versus Transcatheter Aortic Valve Replacement: An Updated Meta-Analysis and Systematic Review.

OBJECTIVE: Transcatheter aortic valve replacement (TAVR) has arisen as a viable alternative to surgery. Similarly, minimally invasive surgical aortic valve replacement (mini-SAVR), such as ministernotomy and minithoracotomy, have also gained interest. We conducted a pairwise meta-analysis to further investigate the efficacy of TAVR versus mini-SAVR. METHODS: Medical databases were comprehensively searched for studies comparing TAVR with a mini-SAVR modality, defined as minimally invasive aortic surgery, ministernotomy, minithoracotomy, or rapid-deployment or sutureless SAVR. Random-effects meta-analysis was conducted using the generic inverse variance method. Primary outcomes included 30-day mortality, midterm mortality, 30-day stroke, acute kidney injury (AKI), paravalvular leak (PVL), new permanent pacemaker (PPM), new-onset atrial fibrillation, and postintervention mean and peak valve pressure gradients and were pooled as risk ratio (RR), mean difference (MD), or hazard ratio (HR) with 95% confidence interval (CI). RESULTS: A total of 5,071 patients (2,505 mini-SAVR vs 2,566 TAVR) from 12 studies were pooled. Compared with TAVR, mini-SAVR showed significantly lower rates of both 30-day (RR = 0.63, 95% CI: 0.42 to 0.96, P = 0.03) and midterm mortality at 4 years of follow-up (HR = 0.76, 95% CI: 0.67 to 0.87, P < 0.001). Furthermore, mini-SAVR was protective against 30-day PVL (RR = 0.07, 95% CI: 0.04 to 0.13, P < 0.001) and new PPM (RR = 0.25, 95% CI: 0.11 to 0.57, P < 0.001). Conversely, TAVR was protective against 30-day AKI (RR = 1.67, 95% CI: 1.20 to 2.32, P = 0.002) and postinterventional mean gradients (MD = 1.65, 95% CI: 0.25 to 3.05, P = 0.02). No difference was observed for 30-day stroke (RR = 0.84, 95% CI: 0.56 to 1.24, P = 0.38), new-onset atrial fibrillation (RR = 1.79, 95% CI: 0.93 to 3.44, P = 0.08), or postinterventional peak gradients (MD = 3.24, 95% CI: -1.10 to 7.59, P = 0.14). CONCLUSIONS: Compared with TAVR, mini-SAVR was protective against 30-day and midterm mortality, 30-day PVL, and new permanent pacemaker, while TAVR patients had lower 30-day AKI. Future randomized trials comparing the efficacy of mini-SAVR approaches with TAVR are needed.

Ross procedure versus pulmonary homograft versus mechanical valve versus bioprosthetic valve versus Ozaki procedure for surgical aortic valve replacement: a frequentist network meta-analysis.

BACKGROUND: There has been a resurgence in interest regarding the Ross procedure due to recent publications detailing positive long-term outcomes. Conversely, surgical aortic valve replacement (SAVR) with a pulmonary homograft (PH), mechanical (MV), bioprosthetic (BV), or the Ozaki procedure each has its own technical advantages and disadvantages. Therefore, we performed a network meta-analysis (NMA) comparing other alternatives to Ross procedure. METHODS: Medical databases were comprehensively searched for studies comparing the Ross procedure with AVR using a PH, MV, BV, or the Ozaki procedure. Outcomes were pooled as risk ratios (RR) with their 95% confidence intervals (95% CI). RESULTS: A total of 7816 patients were pooled for our NMA from 24 studies. Compared to Ross procedure, both BV and MV were associated with significantly higher rates of 30-day mortality of RR (2.37, 95% CI 1.20-4.67) and (1.88 95% CI 1.04-3.40), respectively, with no significant difference regarding PH or Ozaki. However, only MV was associated with a higher risk of 30-day stroke (RR 8.42, 95% CI 1.57-45.23) with no significant difference in the other alternatives, as well as 30-day MI which showed no significant differences between any of the aortic conduits compared to the Ross procedure. Regarding 30-day major bleeding, MV was associated with a higher when compared to the Ross procedure RR (4.58, 95% CI 1.94-10.85), PH was associated with a lower risk of major bleeding with RR (0.35, 95% CI 0.17-0.71), and BV showed no significant difference. With a mean follow-up duration of 8.5 years compared to the Ross procedure, BV, PH, and MV were associated with a higher risk of long-term mortality with RR (1.89, 95% CI 1.38-2.58), (1.38, 95% CI 1.0-1.87), and (1.94, 95% CI 1.52-2.47), respectively, with the Ozaki procedure showed no significant difference. Regarding long-term stroke-with a mean of 6.3-year follow-up duration-there were no significant differences between any of the aortic conduits compared to the Ross procedure. Nevertheless, long-term need for reintervention-with a mean follow-up duration of 17.5 years-was significant of higher risk with both BV and PH with RR (3.28, 95% CI 1.21-8.84) and (2.42, 95% CI 1.05-5.58), respectively, compared to Ross procedure with MV and Ozaki having no significant difference. CONCLUSIONS: The Ross procedure is a viable treatment option for patients undergoing SAVR, showing promising outcomes at short- and long-term follow-ups.

Opioid-free anesthesia versus opioid-based anesthesia in patients undergoing cardiovascular and thoracic surgery: a meta-analysis and systematic review.

BACKGROUND: Despite their extensive clinical use, opioids are characterized by several side effects. These complications, coupled with the ongoing opioid epidemic, have favored the rise of opioid-free-anesthesia (OFA). Herein, we perform the first pairwise meta-analysis of clinical outcomes for OFA vs opioid-based anesthesia (OBA) in patients undergoing cardiovascular and thoracic surgery. METHODS: We comprehensively searched medical databases to identify studies comparing OFA and OBA in patients undergoing cardiovascular or thoracic surgery. Pairwise meta-analysis was performed using the Mantel-Haenszel method. Outcomes were pooled as risk ratios (RR) or standard mean differences (SMD) and their 95% confidence intervals (95% CI). RESULTS: Our pooled analysis included 919 patients (8 studies), of whom 488 underwent surgery with OBA and 431 with OFA. Among cardiovascular surgery patients, compared to OBA, OFA was associated with significantly reduced post-operative nausea and vomiting (RR, 0.57; P = .042), inotrope need (RR .84, P = .045), and non-invasive ventilation (RR, .54; P = .028). However, no differences were observed for 24hr pain score (SMD, -.35; P = .510) or 48hr morphine equivalent consumption (SMD, -1.09; P = .139). Among thoracic surgery patients, there was no difference between OFA and OBA for any of the explored outcomes, including post-operative nausea and vomiting (RR, 0.41; P = .025). CONCLUSION: Through the first pooled analysis of OBA vs OFA in a cardiothoracic-exclusive cohort, we found no significant difference in any of the pooled outcomes for thoracic surgery patients. Although limited to 2 cardiovascular surgery studies, OFA was associated with significantly reduced postoperative nausea and vomiting, inotrope need, and non-invasive ventilation in these patients. With growing use of OFA in invasive operations, further studies are needed to assess their efficacy and safety in cardiothoracic patients.

Shortened strongylid egg reappearance periods in horses following macrocyclic lactone administration - The impact on parasite dynamics.

Over the past three decades, equine strongylid egg reappearance periods (ERPs) have shortened substantially for macrocyclic lactone anthelmintics. The ERPs of ivermectin and moxidectin were originally reported in the 8-10 and 12-16 week ranges, respectively, but several recent studies have found them to be around 4-5 weeks for both actives. This loss of several weeks of suppressed strongylid egg output could have substantial implications for parasite control. This study made use of a computer simulation model to evaluate the impact of shortened ERPs on the anthelmintic performance of ivermectin and moxidectin against equine cyathostomins. The original ERPs were set to 7.1 and 15.4 weeks for ivermectin and moxidectin, respectively, while the reduced ERP was set to 4.6 weeks for both actives. Simulations were set to compare model outputs between original and reduced ERP scenarios and results expressed as percent increase in strongylid egg output, infective third stage larvae on herbage (L3h), and encysted early third stage larvae (EL3). For each drug, simulations were evaluated for two different treatment scenarios (2 and 4 treatments annually), two different age groups (yearlings and adults), and for four different climates (cold humid continental, temperate oceanic, humid subtropical, and hot/cold semi-arid). Across all simulations, there was a substantial increase of the three evaluated parameters. With the ivermectin simulations, all three parameters increased in the 100-300% range across climates, age groups and treatment intensities. The moxidectin simulations displayed a wider range of results with parameters increasing from a few hundred to several thousand percent. The increases were most pronounced for L3h in the two cooler climates, reaching as high as 6727%. Overall, the loss of anthelmintic performance was at a magnitude of 10 times larger for moxidectin compared to ivermectin. This performance loss was climate dependent, and was also affected by treatment intensity, but not by horse age. This is the first study to evaluate consequences of shortened ERPs in horses and demonstrated a substantial loss in anthelmintic performance resulting from this development. The results illustrate that anthelmintic efficacy is more than the percent reduction of fecal egg counts at 14 days post treatment, and that substantial anthelmintic performance can be lost despite FECRTs remaining at 100%.

Year in Review: Long COVID and Pulmonary Rehabilitation.

There have been an estimated 100 million people diagnosed with COVID-19 in the United States, with a majority of patients reporting persistent symptoms expressed as long COVID. The 2 most frequently reported long COVID symptoms are shortness of breath and fatigue. Exercise training during pulmonary rehabilitation (PR) is a successful strategy for improving the lives of people with persistent respiratory symptoms caused by a variety of lung diseases. This narrative review assessed the impact of exercise interventions on functional exercise capacity measures and related symptoms (dyspnea, fatigue) in people with long COVID over the last year. Articles were accessed through electronic databases including PubMed, Embase, CINAHL Plus with full text (EBSCO), and LitCovid. Findings for this Year in Review revealed that exercise interventions and PR show promise for improving functional exercise capacity, dyspnea, and fatigue in people with long COVID. This review supports the need for more rigorous scientific studies on the benefits of structured PR in people with long COVID who have respiratory-related symptoms.