Effectiveness of Topical Antibiotics in Treating Corals Affected by Stony Coral Tissue Loss Disease

Since 2014, Stony Coral Tissue Loss Disease (SCTLD) has led to mass mortality of the majority of hard coral species on the Florida Reef Tract. Following the successful treatment of SCTLD lesions on laboratory corals using water dosed with antibiotics, two topical pastes were developed as vehicles to directly apply antibiotic treatments to wild corals. These pastes were tested as placebos and with additions of amoxicillin on active SCTLD lesions on multiple coral species. The effectiveness of the pastes without antibiotics (placebo treatments) was 4% and 9%, no different from untreated controls. Adding amoxicillin to both pastes significantly increased effectiveness to 70% and 84%. Effectiveness with this method was seen across five different coral species, with success rates of the more effective paste ranging from 67% (Colpophyllia natans) to 90% (Orbicella faveolata and Montastraea cavernosa). Topical antibiotic application is a viable and effective tool for halting disease lesions on corals affected by SCTLD

Short- and Long-Term Effectiveness of Coral Disease Treatments

Since 2014, stony coral tissue loss disease (SCTLD) has led to large-scale mortality of over 20 coral species throughout the Florida Reef Tract. In 2019, in-water disease intervention strategies were implemented to treat affected corals. Two treatment strategies were employed: (1) topical application of an amoxicillin paste directly to disease margins, and (2) application of a chlorinated epoxy to disease margins as well as an adjacent “disease break” trench. Effectiveness of treatments on 2,379 lesions from 725 corals representing five species was evaluated using mixed effects logistic regression models which demonstrated substantially greater effectiveness of amoxicillin compared to chlorine-treated lesions across all species up to 3 months post-treatment. As a result of the failed chlorinated epoxy treatments, any new lesions that appeared during subsequent monitoring events were treated with amoxicillin paste, and all corals were monitored and treated as needed approximately every 2 months for up to 24 months. The health status of 1664 amoxicillin-treated corals during each monitoring event was used to model the probability of a coral being uninfected over time. Models included species and geographic regions as variables. The appearance of new lesions (reinfection rates) varied by species, and offshore sites showed greater reinfection rates than inshore sites; however, all sites and species exhibited a decreased probability of reinfection with time since initial treatment. We conclude that topical amoxicillin treatments are highly effective at halting SCTLD lesions and that through initial and follow-up treatments as needed, colonies and reef sites will progress toward a lower prevalence of SCTLD

Outcomes of primary care delivery by nurse practitioners: Utilization, cost, and quality of care

ObjectiveTo examine whether nurse practitioner (NP)- assigned patients exhibited differences in utilization, costs, and clinical outcomes compared to medical doctor (MD)- assigned patients.Data SourcesVeterans Affairs (VA) administrative data capturing characteristics, outcomes, and provider assignments of 806 434 VA patients assigned to an MD primary care provider (PCP) who left VA practice between 2010 and 2012.Study DesignWe applied a difference- in- difference approach comparing outcomes between patients reassigned to MD and NP PCPs, respectively. We examined measures of outpatient (primary care, specialty care, and mental health) and inpatient (total and ambulatory care sensitive hospitalizations) utilization, costs (outpatient, inpatient and total), and clinical outcomes (control of hemoglobin A1c, LDL, and blood pressure) in the year following reassignment.Principal FindingsCompared to MD- assigned patients, NP- assigned patients were less likely to use primary care and specialty care services and incurred fewer total and ambulatory care sensitive hospitalizations. Differences in costs, clinical outcomes, and receipt of diagnostic tests between groups were not statistically significant.ConclusionsPatients reassigned to NPs experienced similar outcomes and incurred less utilization at comparable cost relative to MD patients. NPs may offer a cost- effective approach to addressing anticipated shortages of primary care physicians.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154625/1/hesr13246_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154625/2/hesr13246-sup-0001-Authormatrix.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154625/3/hesr13246.pd

Comparable, but distinct: Perceptions of primary care provided by physicians and nurse practitioners in full and restricted practice authority states

AimsTo understand patients- and providers- perceptions of primary care delivered by nurse practitioners (NPs) in the Veterans Affairs Healthcare System.DesignQualitative exploratory study (in convergent mixed- methods design).MethodsSemi- structured interviews in 2016 with primary care providers and patients from facilities in states with full and restricted practice authority for NPs. Patient sample based on reassignment to: (a) a NP; or (b) a different physician following an established physician relationship. Data were analysed using content analysis.ResultsWe interviewed 28 patients, 17 physicians and 14 NPs. We found: (a) NPs provided more holistic care than physicians; (b) patients were satisfied with NPs; and (c) providers- professional experience outweighed provider type.ConclusionsPatients- preferences for NPs (compared with prior physicians) contributed to perceptions of patient centredness. Similarities in providers- perceptions suggest NPs and physicians are both viable providers for primary care.ImpactNurse Practitioners (NPs): practice authorityVeterans Affairs Health care: nurse practitioners will continue to be a viable resource for primary care deliveryUnited States Health care: challenges notions patients may not be satisfied with care provided by NPs and supports expanding their use to provide much- needed access to primary care services; expanding Full Practice Authority would allow states to provide acceptable primary care without diminishing patient or provider experiencesæ è¦ ç ®æ  äº è§£æ £è å å »ç æ ºæ 对é ä¼ å äººå »ç ä¿ å ¥ç³»ç» ä¸­æ ¤ç å¸ æ ä¾ å çº§æ ¤ç ç ç æ³ ã è®¾è®¡æ ¢ç´¢æ §ç å® æ §ç  ç©¶(æ ¶æ æ··å æ ¹æ³ è®¾è®¡)ã æ ¹æ³ 2016å¹´è¿ è¡ ç å ç» æ å è®¿è° ,é è®¿äº å· å æ ¥æ æ ¤ç å¸ ç å ¨ç§ å é å ¨ç§ æ §ä¸ æ ºæ ç å çº§æ ¤ç æ ä¾ è å æ £è ã é æ °å é æ £è æ ·æ ¬:(a) ä¸ å æ ¤ç å¸ ;æ (b)ç¡®ç« å »ç å ³ç³»ç å ¦ä¸ å å »ç ã é ç ¨å 容å æ æ³ å¯¹æ °æ ®è¿ è¡ å æ ã ç» æ æ 们é è®¿äº 28å æ £è ,17å å »ç å 14å æ ¤ç å¸ ã æ 们å ç °:(a)æ ¤ç å¸ æ¯ å »ç æ ä¾ ç æ ¤ç æ ´å ¨é ¢;(b)æ £è å¯¹æ ¤ç å¸ æ å °æ»¡æ ;(c)å »ç æ ºæ ç ä¸ ä¸ ç» éª ç æ é æ¯ å »ç æ ºæ ç±»å ç æ é æ ´å¤§ã ç» è®ºæ £è å¯¹æ ¤ç å¸ ç å 好(ä¸ ä»¥å ç å »ç ç ¸æ¯ )æ å ©äº å»ºç« ä»¥æ £è ä¸ºä¸­å¿ ç è®¤ç ¥ã æ ä¾ è ç è§ å¿µç±»ä¼¼,表æ æ ¤ç å¸ å å »ç é ½æ ¯å ¯è¡ ç å çº§æ ¤ç æ ä¾ è ã å½±å - ¢æ ¤ç å¸ :æ §ä¸ æ ºæ - ¢é ä¼ å äººå »ç ä¿ å ¥ç³»ç» :æ ¤ç å¸ å° ç»§ç»­ä½ ä¸ºæ ä¾ å çº§æ ¤ç æ å ¡ç å ¯ç ¨èµ æº ã - ¢ç¾ å ½å «ç ä¿ å ¥:æ æ è§ å¿µ æ £è å ¯è ½ä¸ æ»¡æ ç ±æ ¤ç å¸ æ ä¾ ç æ ¤ç ,å ¶ä¼ æ ¯æ æ ©å¤§ä½¿ç ¨è å ´,以æ ä¾ æ ¥é ç å çº§ä¿ å ¥æ å ¡;æ ©å¤§å ¨ç§ æ §ä¸ æ ºæ å° ä½¿å å· è ½å¤ æ ä¾ å ¯æ ¥å ç å çº§ä¿ å ¥æ å ¡,è ä¸ ä¼ å å¼±æ £è æ æ ä¾ è ç ä½ éª ãPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163369/2/jan14501.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163369/1/jan14501_am.pd

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Randomized Trial of Early Enhanced Parenteral Nutrition and Later Neurodevelopment in Preterm Infants

Retrospective studies indicate that the parenteral provision of calories, proteins, and lipids in the first week of life is associated with improved later neurodevelopment. We aimed to determine whether infants randomized to an enhanced parenteral nutrition protocol had improved developmental outcomes at 4, 12, or 24 months corrected age (CA). In total, 90 preterm infants (&lt;32 weeks gestational age and &lt;1500 g) were randomized to receive enhanced parenteral nutrition (PN) or standard PN during the first week of life. The enhanced group received a higher glucose infusion rate and intralipids. Neurodevelopmental outcomes included pattern-reversal visually evoked potentials (VEP) at 4 months CA (n = 33) and the Bayley Scales of Infant Development (BSID) at 12 (n = 46) and 24 (n = 29) months CA. P100 latency was longer in the intervention group, indicating slower processing speed (145 vs. 178 ms, p = 0.01). This association did not hold in multivariable analysis adjusting for potentially confounding variables. BSID scores were not associated with enhanced PN. Higher enteral energy and protein intake regardless of randomization group were associated with faster processing speed at 4 months CA (p &le; 0.02 for both). Enhanced early PN was not associated with improved neurodevelopment; however, first-week enteral caloric and protein intake were associated with improved speed of processing

Disease Severity and Quality of Life in Patients With Idiopathic Pulmonary Fibrosis: A Cross-Sectional Analysis of the IPF-PRO Registry

Limited data are available on the association between clinically measured disease severity markers and quality of life (QOL) in idiopathic pulmonary fibrosis (IPF). The study examined the associations between objective disease severity metrics and QOL in a contemporary IPF population. This study evaluated baseline data from patients enrolled in the multicenter, US-based Idiopathic Pulmonary Fibrosis Prospective Outcomes Registry between June 2014 and July 2018. Disease severity metrics included FVC % predicted, diffusing capacity for carbon monoxide (Dlco) % predicted, supplemental oxygen use with activity, supplemental oxygen use at rest, and two summary scores (the Gender-Age-Lung Physiology index, based on gender, age, and % predicted values for Dlco and FVC; and the Composite Physiologic Index, based on % predicted values for Dlco, FVC, and FEV ). Multivariable adjusted regression models were used to examine cross-sectional associations between each severity measure and St. George's Respiratory Questionnaire (SGRQ) total score. Among 829 patients with complete SGRQ data, the median (interquartile range) SGRQ score at enrollment was 40 (26-53), with higher scores indicating worse QOL. Modest SGRQ impairments were observed with increasing Gender-Age-Lung Physiology score (2.9 [1.8-4.0] per 1-point increase] and with increasing Composite Physiologic Index scores (3.0 [2.4-3.6] per 5-point increase). Substantial SGRQ impairments were observed for oxygen use with activity (15.6 [12.9-18.2]), oxygen use at rest (16.2 [13.0-19.4]), and decreasing Dlco (5.0 [4.0-6.1] per 10% decrease in % predicted). Objective measures of disease severity, including severity scores, physiologic parameters, and supplemental oxygen use, are associated with worse QOL in patients with IPF. ClinicalTrials.gov; No.: NCT01915511; URL: www.clinicaltrials.gov