Clinical Outcomes in Patients with Phosphate Abnormalities After Cardiac Surgery: A Retrospective Cohort Study.

BACKGROUND: The clinical significance and incidence of phosphate abnormalities in cardiac surgery have not been investigated extensively. We hypothesize that phosphate abnormalities are associated with a longer time to tracheal extubation. METHODS: This was a single-center, retrospective cohort study in patients who underwent nontransplant cardiac surgery with cardiopulmonary bypass between August 2009 and December 2020. Serum phosphate levels were measured within 6 hours of arrival to the intensive care unit (ICU). Select clinical outcomes were extracted from an intramural database: time to tracheal extubation, hospital length of stay, and in-hospital mortality. The lactate level within 6 hours of arrival to the ICU was extracted as well. RESULTS: A total of 2659 patients were included. There were 502 (18.9%) patients who were found to be hypophosphatemic (phosphate <2.5 mg/dL), 1905 (71.6%) had normal phosphate levels (phosphate 2.5-4.5 mg/dL), and 252 (9.5%) were hyperphosphatemic (phosphate >4.5 mg/dL). Hyperphosphatemia was associated with 26% longer time to tracheal extubation (incident rate ratio, 1.26, 95% confidence interval [CI], 10%, 44%, P = .001), 37% longer hospital length of stay (acceleration factor = 0.63, 95% CI, -43% to -30%); P < .001), and increased in-hospital mortality (odds ratio, 4.0; 95% CI, 2.3-7.1; P < .001) when compared to patients with normal phosphate levels. These associations were not found for hypophosphatemia. CONCLUSIONS: Hyperphosphatemia in the immediate postoperative period after cardiac surgery is associated with adverse clinical outcomes. Future studies will need to investigate if actively correcting the phosphate level has an impact on clinical outcomes.

Associated Mortality Risk of Proton Pump Inhibitor Therapy for the Prevention of Stress Ulceration in Intensive Care Unit Patients: A Systematic Review and Meta-analysis.

GOALS: The aim was to systematically evaluate risks and benefits of proton pump inhibitor (PPI) use for stress ulcer prophylaxis in the critically ill patient. BACKGROUND: Whether PPIs increase mortality in the critically ill patient remains controversial. STUDY: Systematic review and meta-analysis of randomized controlled trials (RCTs) and cohort studies with trial sequential analysis, Bayesian sensitivity analysis, and fragility index analysis. RESULTS: A total of 31 studies in 78,009 critically ill adults receiving PPIs versus any comparator were included. PPI use was associated with an increased mortality risk in all studies [19.6% PPI vs. 17.5% comparator; RR: 1.10; 95% confidence interval (CI): 1.02-1.20; P =0.01], in the subgroup of RCTs (19.4% vs. 18.7%; RR: 1.05; 95% CI: 1.0-1.09, P =0.04), but not cohort studies (19.9% vs. 16.7%; RR: 1.12; 95% CI: 0.98-1.28, P =0.09). Results were maintained with a Bayesian sensitivity analysis (RR: 1.13; 95% credible interval: 1.035-1.227) and a fragility index analysis, but not sequential analysis ( P =0.16). RCTs with a higher baseline severity of illness revealed the greatest mortality risk with PPI use (32.1% PPI vs. 29.4% comparator; RR: 1.09; 95% CI: 1.04-1.14; P <0.001). PPI use reduced clinically important bleeding in RCTs (1.4% PPI vs. 2.1% comparator; RR: 0.67; 95% CI: 0.5-0.9; P =0.009) but increased bleeding in cohort studies (2.7% PPI vs. 1.2% comparator; RR: 2.05; 95% CI: 1.2-3.52; P =0.009). PPI use was not associated with a lower incidence of clinically important bleeding when compared with histamine-2 receptor antagonists (1.3% vs. 1.9%; RR: 0.59; 95% CI: 0.28-1.25, P =0.09). CONCLUSIONS: This meta-analysis demonstrated an association between PPI use and an increased risk of mortality.

The Association Between Hypophosphatemia and Lactic Acidosis After Cardiac Surgery With Cardiopulmonary Bypass: A Retrospective Cohort Study.

OBJECTIVES: The clinical significance of hypophosphatemia in cardiac surgery has not been investigated extensively. The aim of this study was to evaluate the association of postoperative hypophosphatemia and lactic acidosis in cardiac surgery patients at the time of intensive care unit (ICU) admission. DESIGN: A retrospective cohort study. SETTING: At a single academic center. PARTICIPANTS: Patients who underwent nontransplant cardiac surgery with cardiopulmonary bypass between August 2009 and December 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serum phosphate and lactate levels were measured upon ICU admission in patients undergoing nontransplant cardiac surgery with cardiopulmonary bypass. There were 681 patients in the low-phosphate (<2.5 mg/dL) group and 2,579 patients in the normal phosphate group (2.5-4.5 mg/dL). A higher proportion of patients in the low phosphate group (26%; 179 of 681; 95% CI: 23-30) had severe lactic acidosis compared to patients in the normal phosphate group (16%; 417 of 2,579; 95% CI: 15-18). In an unadjusted logistic regression model, patients in the low phosphate group had 1.9-times the odds of having severe lactic acidosis (serum lactate ≥4.0 mmol/L) when compared to patients in the normal phosphate group (95% CI: 1.5-2.3), and still 1.4-times the odds (95% CI: 1.1-1.7) after adjusting for several possible confounders. CONCLUSIONS: Hypophosphatemia is associated with lactic acidosis in the immediate postoperative period in cardiac surgery patients. Future studies will need to investigate it as a potential treatment target for lactic acidosis.

Fine wire versus locking plate fixation of type C pilon fractures.

PURPOSE: The successful treatment of high energy pilon fractures (AO-OTA 43C) can be achieved with a fine wire circular external fixator (CEF) or locking plate construct (ORIF). There is no consensus on whether ORIF or CEF achieves superior outcomes, and both have unique complications. We report early to mid-term outcomes comparing type C pilon fractures treated with ORIF and CEF. METHODS: An 8-year retrospective review was performed on all patients who underwent ORIF or CEF for closed 43C fractures in a tertiary orthoplastic centre. Outcomes included unplanned return to theatre prior to union including superficial and deep surgical site infections (SSI), non-union and post-traumatic osteoarthritis (PTOA) needing fusion. RESULTS: 76 patients underwent ORIF and 59 patients had CEF, with a mean follow-up of 2 years. 7/76 (9.2%) patients who underwent ORIF had a superficial SSI; 2 patients (2.6%) required a formal debridement for deep SSI; none required a flap. 13/59 patients (22%) had a pin track infection following CEF. With the numbers available, there was no significant difference in rates of unplanned return to theatre before bone healing (ORIF 7/76, 9.2%, CEF 9/59, 15.2%, p = 0.7), rates of mal-union (1.7% CEF, 3.9% ORIF, p = 0.7), deep SSI (p = 0.9), time to union (ORIF: 8.1 months v CEF 10.8 months, p = 0.51), non-union (p = 0.24) and fusion for PTOA (ORIF: 6/76, CEF 2/59, p = 0.46). CONCLUSION: With correct patient selection, both ORIF and CEF offer equivalent and favourable early to mid-term outcomes with regard to deep SSI, non-union, mal-union and PTOA. Although statistically insignificant, ORIF with more than 2 plates carries a risk of superficial and deep SSI, whilst CEF is associated with a 22% pin track infection rate. These unique risks must be discussed with the patient as part of a shared decision-making process.

Seizure Occurring During Baclofen Monotherapy for Phenibut Withdrawal.

OBJECTIVE: Phenibut is a widely available gamma-aminobutyric acid B receptor agonist. When taken chronically, phenibut causes dependence and subsequent withdrawal if stopped. Baclofen, a gamma-aminobutyric acid B receptor agonist structurally related to phenibut, has been used to manage phenibut withdrawal (PW), although baclofen doses for PW are not well defined and may exceed Food and Drug Administration-approved doses. Little data described outcomes from baclofen use. METHODS: This case details a patient who experienced a seizure while on baclofen 10 mg thrice daily as monotherapy for PW and highlights a potential risk of underdosing baclofen as monotherapy in the management of PW. RESULTS: A man in his early 30s with anxiety, depression, and substance use disorder presented to the emergency department by family for lethargy and confusion starting earlier that day. He had been using 25-30 g of phenibut daily for the past 6 months. On arrival, he was hypertensive, tachycardic, tachypneic, and lethargic. The patient received 1 mg of intravenous lorazepam and was admitted to the hospital for presumed PW. His symptoms improved overnight, and he was discharged on 10 mg of baclofen thrice daily. He returned 28 hours later after having a seizure and required intensive care admission in addition to multimodal drug therapy. CONCLUSIONS: Phenibut use is rising, and treatment options for PW, such as baclofen, warrant additional study. Potential risks of underdosing baclofen if used as monotherapy in PW may include seizures as withdrawal progresses. Baclofen's role in therapy may be more appropriate as an adjunct than a cornerstone of therapy. Treatment done in consultation with providers experienced in managing withdrawal such as a toxicologist may help reduce this risk.

Sustained Effect of Clinical Decision Support for Heart Failure: A Natural Experiment Using Implementation Science.

OBJECTIVES: In a randomized controlled trial, we found that applying implementation science (IS) methods and best practices in clinical decision support (CDS) design to create a locally customized, "enhanced" CDS significantly improved evidence-based prescribing of ß blockers (BB) for heart failure compared with an unmodified commercially available CDS. At trial conclusion, the enhanced CDS was expanded to all sites. The purpose of this study was to evaluate the real-world sustained effect of the enhanced CDS compared with the commercial CDS. METHODS: In this natural experiment of 28 primary care clinics, we compared clinics exposed to the commercial CDS (preperiod) to clinics exposed to the enhanced CDS (both periods). The primary effectiveness outcome was the proportion of alerts resulting in a BB prescription. Secondary outcomes included patient reach and clinician adoption (dismissals). RESULTS: There were 367 alerts for 183 unique patients and 171 unique clinicians (pre: March 2019-August 2019; post: October 2019-March 2020). The enhanced CDS increased prescribing by 26.1% compared with the commercial (95% confidence interval [CI]: 17.0-35.1%), which is consistent with the 24% increase in the previous study. The odds of adopting the enhanced CDS was 81% compared with 29% with the commercial (odds ratio: 4.17, 95% CI: 1.96-8.85). The enhanced CDS adoption and effectiveness rates were 62 and 14% in the preperiod and 92 and 10% in the postperiod. CONCLUSION: Applying IS methods with CDS best practices was associated with improved and sustained clinician adoption and effectiveness compared with a commercially available CDS tool.

Extraction Free RT-PCR Surveillance Testing and Reporting for SARS-CoV-2.

The COVID-19 pandemic necessitated sensitive, fast and inexpensive testing for the virus on university campuses across the nation in 2020 prior to the widespread availability of vaccines. Early testing efforts were limited by bottlenecks on reagents, low throughput testing options and slow return of test results. In this paper we detail the testing pipeline we established at the University of Wisconsin-Madison for rapid, inexpensive and sensitive surveillance testing for SARS-CoV-2 and highlight the strengths of the platform that would allow it to be applied to other disease surveillance projects, SARS-CoV-2 variant testing or future pandemics.

Development and content validation of a competency-based assessment tool for penile prosthesis surgery.

The aim of this study was to identify potential hazards for the inflatable penile prosthesis (IPP) surgical procedure and from this develop and content validate an IPP intraoperative competency-based assessment tool. A multi-institutional longitudinal prospective observational study was conducted over a 6-month period. Healthcare Failure Mode and Effects Analysis (HFMEA) methodology was used to prospectively risk assess the IPP procedure using a collaborative multidisciplinary team (MDT) approach. International content validation of the developed tool was then undertaken via face-to-face meetings and WebEx seminars. A total of 22 h of observation led to the construction of a detailed process map consisting of 11 stages and 49 sub-stages. HFMEA identified 50 failure modes and 45 failure mode effects, nine failure modes were excluded after analysis leaving 41 key failure modes included in the checklist. The high-risk steps identified were related to corporal dilatation, incorrect sizing of the prosthesis cylinders and incorrect localisation of the superficial inguinal ring for blind reservoir placement. The final content validated IPP assessment tool (PPAT) consisted of 13 processes and 27 sub-processes. We concluded that HFMEA methodology successfully allowed for the identification of key steps within the IPP procedure from which the PPAT was developed. Formal international content validation confirmed that all key procedural steps were included in the PPAT and that completion of all steps would indicate trainee competency in the procedure. Further validation is required before the tool can be used to assess learning curves for the IPP procedure.

Complete Genome Sequences of Five Bacteriophages That Infect Enterobacteriales Hosts.

Full genome sequences of five bacteriophages that were isolated from raw sewage samples and infect Enterobacteriales hosts are presented. Brookers is a P22-like Proteus phage, OddieOddie is a 9g-like Escherichia coli phage, Diencephelon is a Kp3-like Klebsiella phage, and Rgz1 and Lilpapawes are classic T4-like and T7-like virulent Proteus phages, respectively.

Follicle flushing does not improve live birth and increases procedure time: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To determine whether follicle flushing during oocyte retrieval improves live birth or secondary outcomes in assisted reproductive technology (ART). DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Women undergoing ART using autologous gametes. INTERVENTION(S): A systematic search of PubMed, EMBASE, Cochrane Database, and Web of Science for randomized controlled trials comparing follicle flushing to direct aspiration during oocyte retrieval published in English between 1989 to 2020. MAIN OUTCOME MEASURE(S): Live birth as primary outcome, and clinical and ongoing pregnancy, total and mature metaphase II (MII) oocytes retrieved, and operating time as secondary outcomes. RESULT(S): Eleven studies were included totaling 1,178 cases. No difference in live birth was demonstrated between follicle flushing and direct aspiration. Clinical pregnancy and ongoing pregnancy were not improved with flushing. Total oocyte and MII yield were lower with flushing compared with direct aspiration. Procedure time was increased with flushing by 2 minutes in poor responders and 9 minutes in normal responders. Other sensitivity analyses did not demonstrate any changes, except the difference in MII yield was no longer statistically significant. CONCLUSION(S): Follicle flushing during oocyte retrieval increases procedure time and does not improve live birth or secondary ART outcomes. Randomized data do not support the use of follicle flushing as an intervention in ART.

Sulfoglycodendrimer Therapeutics for HIV-1 and SARS-CoV-2.

Hexavalent sulfoglycodendrimers (SGDs) are synthesized as mimics of host cell heparan sulfate proteoglycans (HSPGs) to inhibit the early stages in viral binding/entry of HIV-1 and SARS-CoV-2. Using an HIV neutralization assay, the most promising of the seven candidates are found to have sub-micromolar anti-HIV activities. Molecular dynamics simulations are separately implemented to investigate how/where the SGDs interacted with both pathogens. The simulations revealed that the SGDs: 1) develop multivalent binding with polybasic regions within and outside of the V3 loop on glycoprotein 120 (gp120) for HIV-1, and consecutively bind with multiple gp120 subunits, and 2) interact with basic amino acids in both the angiotensin-converting enzyme 2 (ACE2) and HSPG binding regions of the Receptor Binding Domain (RBD) from SARS-CoV-2. These results illustrate the considerable potential of SGDs as inhibitors in viral binding/entry of both HIV-1 and SARS-CoV-2 pathogens, leading the way for further development of this class of molecules as broad-spectrum antiviral agents.

Applying Clinical Decision Support Design Best Practices With the Practical Robust Implementation and Sustainability Model Versus Reliance on Commercially Available Clinical Decision Support Tools: Randomized Controlled Trial.

BACKGROUND: Limited consideration of clinical decision support (CDS) design best practices, such as a user-centered design, is often cited as a key barrier to CDS adoption and effectiveness. The application of CDS best practices is resource intensive; thus, institutions often rely on commercially available CDS tools that are created to meet the generalized needs of many institutions and are not user centered. Beyond resource availability, insufficient guidance on how to address key aspects of implementation, such as contextual factors, may also limit the application of CDS best practices. An implementation science (IS) framework could provide needed guidance and increase the reproducibility of CDS implementations. OBJECTIVE: This study aims to compare the effectiveness of an enhanced CDS tool informed by CDS best practices and an IS framework with a generic, commercially available CDS tool. METHODS: We conducted an explanatory sequential mixed methods study. An IS-enhanced and commercial CDS alert were compared in a cluster randomized trial across 28 primary care clinics. Both alerts aimed to improve beta-blocker prescribing for heart failure. The enhanced alert was informed by CDS best practices and the Practical, Robust, Implementation, and Sustainability Model (PRISM) IS framework, whereas the commercial alert followed vendor-supplied specifications. Following PRISM, the enhanced alert was informed by iterative, multilevel stakeholder input and the dynamic interactions of the internal and external environment. Outcomes aligned with PRISM's evaluation measures, including patient reach, clinician adoption, and changes in prescribing behavior. Clinicians exposed to each alert were interviewed to identify design features that might influence adoption. The interviews were analyzed using a thematic approach. RESULTS: Between March 15 and August 23, 2019, the enhanced alert fired for 61 patients (106 alerts, 87 clinicians) and the commercial alert fired for 26 patients (59 alerts, 31 clinicians). The adoption and effectiveness of the enhanced alert were significantly higher than those of the commercial alert (62% vs 29% alerts adopted, P<.001; 14% vs 0% changed prescribing, P=.006). Of the 21 clinicians interviewed, most stated that they preferred the enhanced alert. CONCLUSIONS: The results of this study suggest that applying CDS best practices with an IS framework to create CDS tools improves implementation success compared with a commercially available tool. TRIAL REGISTRATION: ClinicalTrials.gov NCT04028557; http://clinicaltrials.gov/ct2/show/NCT04028557.

Establishing the Therapeutic Index of Fluid Resuscitation in the Septic Patient: A Narrative Review and Meta-Analysis.

This comprehensive review comparatively evaluates the safety and benefits of parenteral fluids used in resuscitation with a focus on sepsis. It also provides a random-effects meta-analysis of studies comparing restrictive resuscitation and usual care in sepsis with the primary outcome of mortality. In the septic patient, fluid therapy remains a complex interplay between fluid compartments in the body, the integrity of the endothelial barrier, and the inflammatory tone of the patient. Recent data have emerged describing the pharmacokinetics of fluid resuscitation that can be affected by the factors just listed, as well as mean arterial pressure, rate of infusion, volume of fluid infusate, nature of the fluid, and drug interactions. Fluid overload in sepsis has been associated with vasodilation, kidney injury, and increased mortality. Restrictive resuscitation after the initial septic insult is an emerging practice. Our search strategy of Medline databases revealed six randomized studies with 706 patients that examined restrictive resuscitation in sepsis. Results of this meta-analysis demonstrated no differences in mortality with restrictive resuscitation compared with usual care (30.6% vs 37.8%; risk ratio 0.83, 95% confidence interval 0.66-1.05, respectively) but was limited by the small number of studies and larger quantities of pre-randomization fluids. Another approach to address fluid overload is active (diuresis) de-resuscitation strategies that may shorten the need for mechanical ventilation and intensive care unit length of stay. Data suggest that colloids may confer mortality benefit over saline in the most severely ill septic patients. Compared with isotonic saline, balanced resuscitation fluids are associated with a lower incidence of acute kidney injury and mortality. The benefits of balanced resuscitation fluids are most evident when higher volumes of fluids are used for sepsis. Clinicians should consider these pharmacotherapeutic factors when selecting a fluid, its quantity, and rate of infusion.

A systematic review of the long-term efficacy of low-intensity shockwave therapy for vasculogenic erectile dysfunction.

PURPOSE: To look at the evidence base for LISWT as a treatment modality for vasculogenic erectile dysfunction, focusing on the long-term outcomes at over 6 months following treatment. METHODS: A systematic literature search was conducted utilising MEDLINE and Scopus databases from 2010 to September 2018 by two independent reviewers. Outcome measures extracted for long-term efficacy included International Index of Erectile Function scores and Erection Hardness Scores. Subgroup analysis for LISWT effectiveness included age, PDE5i responsiveness, presence of vascular co-morbidities and smoking status. RESULTS: The search identified eleven studies, representing a total of 799 patients. Nine studies found a significant improvement in erectile function after LISWT at 6-month follow-up (median IIEF-EF improvement in 5.3 at 6 months). However, of five studies assessing erectile function at 12 months; two identified a plateauing of results, with three a deterioration (IIEF-EF score changes of - 2 to 0.1 from 6 months). Erectile function did, however, remain above baseline results in all of these studies. Subgroup analysis revealed increasing age to reduce the response to LISWT treatment. Whilst ED severity, PDE5i responsiveness and co-morbidities potentially influence effectiveness, results are still inconsistent. CONCLUSIONS: LISWT may be a safe and acceptable potential ED treatment with demonstrated benefits at 6 months. There is some question regarding efficacy deterioration beyond this, but there is still a demonstrated benefit seen even at 12 months post treatment. However, quality of evidence remains low with larger multiinstitutional studies required, standardising confounders such as shockwave administration and oral medication use.

Does hyperbaric oxygen therapy have the potential to improve salivary gland function in irradiated head and neck cancer patients?

Following radiotherapy, many patients with osteoradionecrosis suffer from xerostomia, thereby decreasing their quality of life. Patients can develop problems with speech, eating, increased dental caries, dysphagia, fractured dentition, chronic refractory osteomyelitis and osteoradionecrosis. Symptoms associated with salivary gland dysfunction can be severe enough that patients terminate the course of their radiotherapy prematurely due to the decrease in their quality of life. Currently, the only treatments available to patients are palliative. A definitive treatment has yet to be discovered. Head and neck cancers, which comprise 5% of overall cancer treatments, rank 8th most expensive to treat in the United States today. Hyperbaric oxygen is being considered for the therapy of radiated salivary glands because it has been shown to stimulate capillary angiogenesis and fibroplasia in radiation treated tissues. It has been hypothesized that salivary acinar cells undergo apoptosis following radiation therapy. The purpose of this paper is to discuss the mechanisms of salivary gland injury and evaluate whether hyperbaric oxygen therapy improves salivary gland function in patients who develop xerostomia and osteoradionecrosis following head and neck radiation.